Search

Biallelic pathogenic variants in the essential DNA repair gene BRCA2 causes Fanconi anemia, complementation group FA-D1. Patients in this group are highly prone to develop embryonal tumors, most commonly medulloblastoma arising from the cerebellar granule cell progenitors (GCPs). GCPs undergo high proliferation in the postnatal cerebellum under SHH activation, but the type of DNA lesions that require the function of the BRCA2 to prevent tumorigenesis remains unknown. To identify such lesions, we assessed both GCP neurodevelopment and tumor formation using a mouse model with deletion of exons three and four of Brca2 in the central nervous system, coupled with global Trp53 loss. Brca2 Δex3-4 ;Trp53 -/- animals developed SHH subgroup medulloblastomas with complete penetrance. Whole-genome sequencing of the tumors identified structural variants with breakpoints enriched in areas overlapping G-quadruplexes (G4s). Brca2 -deficient GCPs exhibited decreased replication speed in the presence of the G4-stabilizer pyridostatin. Pif1 helicase, which resolves G4s during replication, was highly upregulated in tumors, and Pif1 knockout in primary MB tumor cells resulted in increased genome instability upon pyridostatin treatment. These data suggest that G4s may represent sites prone to replication stalling in highly proliferative GCPs and without BRCA2, G4s become a source of genome instability. Tumor cells upregulate G4-resolving helicases to facilitate rapid proliferation through G4s highlighting PIF1 helicase as a potential therapeutic target for treatment of BRCA2 -deficient medulloblastomas., Competing Interests: Competing Interest Statement A.S. is an advisor to Rocket Pharmaceuticals. Other authors have declared that no conflict of interest exists.

Optimizing the treatment of hydrocephalus remains a major challenge in adult and pediatric neurosurgery. Currently, clinical treatment relies heavily on anatomic imaging of ventricular size and clinical presentation. The emergence of functional and structural brain connectivity imaging has provided the basis for a new paradigm in the management of hydrocephalus. Here we review the pertinent advances in this field. Following PRISMA-ScR guidelines for scoping reviews, we searched PubMed for relevant literature from 1994 to April 2023 using hydrocephalus and MRI-related terms. Included articles reported original MRI data on human subjects with hydrocephalus, while excluding non-English or pre-1994 publications that didn't match the study framework. The review identified 44 studies that investigated functional and/or structural connectivity using various MRI techniques across different hydrocephalus populations. While there is significant heterogeneity in imaging technology and connectivity analysis, there is broad consensus in the literature that 1) hydrocephalus is associated with disruption of functional and structural connectivity, 2) this disruption in cerebral connectivity can be further associated with neurologic compromise 3) timely treatment of hydrocephalus restores both cerebral connectivity and neurologic compromise. The robustness and consistency of these findings vary as a function of patient age, hydrocephalus etiology, and the connectivity region of interest studied. Functional and structural brain connectivity imaging shows potential as an imaging biomarker that may facilitate optimization of hydrocephalus treatment. Future research should focus on standardizing regions of interest as well as identifying connectivity analysis most pertinent to clinical outcome., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Craniovertebral junction (CVJ) abnormalities are common and well documented in mucopolysaccharidosis type I-Hurler syndrome (MPS IH), often causing severe spinal canal narrowing. However, the requirement for surgical decompression and/or fusion is uncommon. Although hematopoietic cell transplant (HCT) has been shown to prolong the lives of patients with MPS IH, its effect in halting or reversing musculoskeletal abnormalities is less clear. Unfortunately, there are currently no universal guidelines for imaging or indication for surgical interventions in these patients. The goal of this study was to track the progression of the CVJ anatomy in patients with MPS IH following HCT, and to examine radiographic features in patients who needed surgical intervention., Methods: Patients with MPS IH treated at the University of Minnesota with allogeneic HCT between 2008 and 2020 were retrospectively reviewed. Patients who underwent CVJ surgery were identified with chart review. All MPS IH cervical scans were examined, and the odontoid retroflexion angle, clivoaxial angle (CXA), canal width, and Grabb-Oakes distance (pB-C2) were measured yearly for up to 7 years after HCT. Longitudinal models based on the measurements were made. An intraclass correlation coefficient was used to measure interrater reliability. Nine children without MPS IH were examined for control CVJ measurements., Results: A total of 253 cervical spine MRI scans were reviewed in 54 patients with MPS IH. Only 4 (7.4%) patients in the study cohort required surgery. Three of them had posterior fossa and C1 decompression, and 1 had a C1-2 fusion. There was no statistically significant difference in the spinal parameters that were examined between surgery and nonsurgery groups. Among the measurements, canal width and CXA varied drastically in patients with different neck positions. Odontoid retroflexion angle and CXA tended to decrease with age. Canal width and pB-C2 tended to increase with age., Conclusions: Based on the data, the authors observed an increase in canal width and pB-C2, whereas the CXA and odontoid retroflexion angle became more acute as the patients aged after HCT. The longitudinal models derived from these data mirrored the development in children without MPS IH. Spinal measurements obtained on MR images alone are not sufficient in identifying patients who require surgical intervention. Symptom monitoring and clinical examination, as well as pathological spinal cord changes on MRI, are more crucial in assessing the need for surgery than is obtaining serial imaging.

Objective: Training of international medical graduates (IMGs) offers opportunities for the US neurosurgery community to engage the global talent pool and impact national and international healthcare. Here, the authors analyzed the time trend of IMGs matching into US neurosurgery programs and identified potential opportunities for enhancing IMG engagement., Methods: The authors analyzed the National Resident Matching Program (NRMP) match results, NRMP program director (PD) surveys, and applicant surveys from 2013 to 2022. Regression methods were used to analyze time trends., Results: Between 2013 and 2022, the number of US neurosurgery residency positions increased by 17.6% (from 204 to 240). During this period, the percentage of IMGs matching into neurosurgery increased from 3.5% to 7%, translating into a 6.8% increase in the likelihood of a successful IMG match per year (95% CI 0.3%-13.8%, p = 0.042). The likelihoods of a successful match for US MDs and IMGs scoring > 260 on the USMLE Step 1 were > 90% and approximately 55%, respectively. In PD surveys, approximately 90% of PDs indicated that they seldom/never interview or rank IMGs. In terms of factors that influenced the PD decision for interviewing/ranking, IMGs are disadvantaged in several categories, including the ability to secure an audition elective/rotation, and proper letters of recommendation, as well as the influence of the culture on the preconceived perception of poor interpersonal skills., Conclusions: The number of IMGs matching successfully in neurosurgery has increased marginally during the past decade. The authors outline the challenges that IMGs encounter in this process and suggest strategies for considerations of IMG training in NRMP-associated institutions.

In recent years, the endoscopic endonasal approach (EEA) for craniopharyngiomas has proven to be a safe option for extensive tumor resection, with minimal or no manipulation of the optic nerves and excellent visualization of the superior hypophyseal branches when compared to the Transcranial Approach (TCA). However, there is an ongoing debate regarding the criteria for selecting different approaches. To explore the current results of EEA and discuss its role in the management of craniopharyngiomas, we performed MEDLINE, Embase, and LILACS searches from 2012 to 2022. Baseline characteristics, the extent of resection, and clinical outcomes were evaluated. Statistical analysis was performed through an X 2 and Fisher exact test, and a comparison between quantitative variables through a Kruskal-Wallis and verified with post hoc Bonferroni. The tumor volume was similar in both groups (EEA 11.92 cm 3 , -TCA 13.23 cm 3 ). The mean follow-up in months was 39.9 for EEA and 43.94 for TCA, p = 0.76). The EEA group presented a higher visual improvement rate (41.96% vs. 25% for TCA, p < 0.0001, OR 7.7). Permanent DI was less frequent with EEA (29.20% vs. 67.40% for TCA, p < 0.0001, OR 0.2). CSF Leaks occurred more frequently with EEA (9.94% vs. 0.70% for TCA, p < 0.0001, OR 15.8). Recurrence rates were lower in the EEA group (EEA 15.50% vs. for TCA 21.20%, p = 0.04, OR 0.7). Our results demonstrate that, in selected cases, EEA for resection of craniopharyngiomas is associated with better results regarding visual preservation and extent of tumor resection. Postoperative CSF leak rates associated with EEA have improved compared to the historical series. The decision-making process should consider each person's characteristics; however, it is noticeable that recent data regarding EEA justify its widespread application as a first-line approach in centers of excellence for skull base surgery.

Competing Interests: All authors have no conflicts of interest to disclose.

Background: Moyamoya is managed by surgical revascularization, but no standardized method has yet been universally adopted., Objective: To describe a new indirect bypass technique for pediatric moyamoya, wide arterial sparing encephalo-duro-synangiosis (WASEDS), which provides a much wider area of revascularization with minimal compromise to the middle meningeal arterial tree compared with traditional procedures. Initially used as a salvage technique after failed encephalo-duro-arterio-synangiosis, its success later motivated its use as a first-line procedure., Methods: Clinical and radiographic records of patients who underwent WASEDS for moyamoya from 2009 to 2020 were reviewed. Brain perfusion relative cerebral blood volume on the side of the WASEDS procedure was calculated. Two-tailed paired t tests were performed to identify the statistically significant differences ( P ≤ .05)., Results: WASEDS was successfully performed on 8 patients for a total of 14 cerebral hemispheres. Age ranged from 2 to 25 years. There were no mortalities. The average clinical and radiographic follow-up was 49.79 months (range 2-126 months), demonstrating improvement in neurological condition and no postoperative stroke and significant diminution or cessation of transient ischemic attacks in all patients. Relative cerebral blood volume increased 9.24% after the WASEDS procedure ( P = .012). There were no neurological complications. There were 2 pseudomeningoceles related to the extensive dural openings., Conclusion: WASEDS is a safe and effective indirect revascularization technique for both primary and salvage techniques. It provides an extensive area of cortical revascularization with no compromise of the middle meningeal vasculature and subjective reports of early improvement in cognition and behavior. The main disadvantage is elevated risk of pseudomeningocele secondary to the large craniotomy., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Objective: Quality improvement (QI) is a methodology used to implement sustainable, meaningful change to improve patient outcomes. Given the complex pathologies observed in pediatric neurosurgery, QI projects could potentially improve patient care. Overall, there is a need to characterize the degree of QI opportunities, training, and initiatives within the field of pediatric neurosurgery. Herein the authors aimed to define the current QI landscape in pediatric neurosurgery., Methods: A cross-sectional survey was sent to all members of the American Association of Neurological Surgeons/Congress of Neurological Surgeons Joint Section on Pediatric Neurological Surgery via email. The responses were anonymized. Questions addressed several relatable QI topics including 1) training and participation in QI; 2) QI infrastructure; 3) QI program incentives; and 4) general opinions on the National Surgical Quality Improvement Program (NSQIP) database, various QI topics, and QI productivity., Results: Responses were received from 129 participants (20% response rate). Most respondents practiced in an academic setting (59.8%) and at a free-standing pediatric hospital (65.4%). Participation in QI projects was high (81.7%), but only 23.8% of respondents had formal QI training. Only 36.5% of respondents had institutional requirements for QI work; the majority of those were only required to participate as a project team member. Nearly half of the respondents did not receive incentives or institutional support for QI. The majority agreed ("strongly" and "somewhat") that a QI course would be beneficial (75.5%), that QI projects should be considered for publication in neurosurgery journals (88.1%), and that there is a need for national quality metrics (81.4%). Over 88% have an interest in seeing QI project presentations at the annual Pediatric Joint Section meeting. Only 26.3% believed that the NSQIP was a useful QI guide. Respondents suggested further study of the following QI topics: overall rates of infection and their prevention, hydrocephalus, standardized treatment algorithms for common disorders, team communication, pediatric neurosurgery-specific database, access to care, and interprofessional education., Conclusions: Areas of opportunity include specialty-specific QI education, tactics for obtaining support to build the QI infrastructure, increased visibility of QI work within pediatric neurosurgery, and a review of available registries to provide readily available data relevant to this specialty.

Background: Ventriculoperitoneal shunt placement is the mainstay of treatment for hydrocephalus, but there are relatively high rates of malfunction. Shunt catheter entry can be performed anteriorly or posteriorly, with the body of evidence from randomized controlled trials and retrospective studies suggesting conflicting findings., Methods: A systematic review of PubMed, Medline, Scopus, and Web of Science was performed adherent to PRISMA guidelines, searching for clinical studies examining outcomes for anterior or frontal and posterior or occipital ventriculoperitoneal shunt placement. A random-effects model meta-analysis was performed on R., Results: Six studies (2 randomized controlled trials and 4 retrospective cohort studies) comprising 1808 patients were identified. There were no statistically significant differences between anterior and posterior ventriculoperitoneal shunt placement for the outcomes of poor catheter placement (odds ratio [OR], 0.74; P = 0.6) and shunt infections (OR, 1.01; P = 0.9). Posterior shunts trended toward greater number of shunt revisions (OR, 0.72; P = 0.06). Six and 12 months shunt survival was comparable between anterior and posterior approaches (P > 0.05). There were significant differences between long-term shunt survival (2 and 5 years shunt survival), favoring anterior shunt placement with greater odds of survival (OR, 1.91 and OR, 1.62, respectively; P < 0.05)., Conclusions: We show that although anteriorly and posteriorly placed shunts have mostly comparable outcomes, shunt survival at 2-year and 5-year intervals favors anteriorly placed shunts. Additional well-designed clinical trials are needed to validate the findings of greater late shunt failure in posteriorly placed shunts, with more time-dependent statistical measures., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: When noninvasive modalities fail to adequately localize the seizure onset zone (SOZ) in children with medically refractory epilepsy, invasive interrogation with stereo-electroencephalography (SEEG) or subdural electrodes may be required. Our center utilizes SEEG for invasive monitoring in a carefully selected population of children, many of whom have seizures despite a prior surgical resection. We describe the cohort of patients who underwent SEEG in the first 5 years of its employment in our institution, almost half of which had a history of a failed epilepsy surgery., Methods: We retrospectively reviewed the records of the first 44 consecutive children who underwent SEEG at Nicklaus Children's Hospital (Miami, Florida), a large, level 4 epilepsy referral center. Patient demographic, clinical, radiographic, and electrophysiological information was collected prospectively. Student's t-test was used for sampling of means and analysis of variance (ANOVA) for evaluation of variance beyond 2 means; chi-square test of independence was used to assess the relationship between categorical variables., Results: There were 44 patients in this cohort, of whom 17 (38.6 %) were male. The mean age of seizure onset was 6.2 years. Twenty-one patients (47.7 %) had previously failed an epilepsy surgery. Patients with a history of prior epilepsy surgery failure were older at SEEG implantation (17.6 vs. 13.7 years; p = 0.043), were more likely to have SEEG for identification of resection margins (9 vs. 4; p = 0.034), and had fewer electrodes placed (5.9 vs. 7.5; p = 0.016). No difference was seen in complication rates between groups with only 3/297 electrodes placed associated with complications, all of which were minor. Post-SEEG, 29 (65.9 %) patients underwent focal resection, 7 patients had VNS insertion, 3 underwent RNS placement, and 5 had no further intervention. The majority of patients that underwent resection in both groups experienced an improvement in seizures (Engel class I-III), reported by 13/15 (86.7 %) in those naive to surgery and 10/14 (71.4 %) in those with prior surgical failure. Seizure-freedom was much lower in those with prior epilepsy surgery, seen in only 4/14 (28.6 %) versus 8/15 (53.3 %)., Conclusion: Our data supports current literature on SEEG as a safe and effective method of electrophysiological evaluation in children naive to surgery and adds that it is a safe technique in children with a history of failed epilepsy surgery. There was no difference in complication rates, which were <1 % in both groups. A favorable outcome was seen in the majority of patients in both groups; the seizure freedom rate, however, was much lower in those with prior epilepsy surgery., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Despite significant advances in diagnostic and surgical techniques, the surgical management of Chiari malformation type I (CM-I) with associated syringomyelia remains controversial, and the type of surgery performed is surgeon dependent. This study's goal was to determine the feasibility of a prospective, multicenter, cohort study for CM-I/syringomyelia patients and to provide pilot data that compare posterior fossa decompression and duraplasty (PFDD) with and without tonsillar reduction., Methods: Participating centers prospectively enrolled children suffering from both CM-I and syringomyelia who were scheduled to undergo surgical decompression. Clinical data were entered into a database preoperatively and at 1-2 weeks, 3-6 months, and 1 year postoperatively. MR images were evaluated by 3 independent, blinded teams of neurosurgeons and neuroradiologists. The primary endpoint was improvement or resolution of the syrinx., Results: Eight clinical sites were chosen based on the results of a published questionnaire intended to remove geographic and surgeon bias. Data from 68 patients were analyzed after exclusions, and complete clinical and imaging records were obtained for 55 and 58 individuals, respectively. There was strong agreement among the 3 radiology teams, and there was no difference in patient demographics among sites, surgeons, or surgery types. Tonsillar reduction was not associated with > 50% syrinx improvement (RR = 1.22, p = 0.39) or any syrinx improvement (RR = 1.00, p = 0.99). There were no surgical complications., Conclusions: This study demonstrated the feasibility of a prospective, multicenter surgical trial in CM-I/syringomyelia and provides pilot data indicating no discernible difference in 1-year outcomes between PFDD with and without tonsillar reduction, with power calculations for larger future studies. In addition, the study revealed important technical factors to consider when setting up future trials. The long-term sequelae of tonsillar reduction have not been addressed and would be an important consideration in future investigations.

Purpose: Magnetic Resonance-guided Laser Interstitial Thermal Therapy (MRgLITT) is an emerging minimally-invasive alternative to resective surgery for medically-intractable epilepsy. The precise lesioning effect produced by MRgLITT supplies opportunities to glean insights into epileptogenic regions and their interactions with functional brain networks. In this exploratory analysis, we sought to characterize associations between MRgLITT ablation zones and large-scale brain networks that portended seizure outcome using resting-state fMRI., Methods: Presurgical fMRI and intraoperatively volumetric structural imaging were obtained, from which the ablation volume was segmented. The network properties of the ablation volume within the brain's large-scale brain networks were characterized using graph theory and compared between children who were and were not rendered seizure-free., Results: Of the seventeen included children, five achieved seizure freedom following MRgLITT. Greater functional connectivity of the ablation volume to canonical resting-state networks was associated with seizure-freedom (p < 0.05, FDR-corrected). The ablated volume in children who subsequently became seizure-free following MRgLITT had significantly greater strength, and eigenvector centrality within the large-scale brain network., Conclusions: These findings provide novel insights into the interaction between epileptogenic cortex and large-scale brain networks. The association between ablation volume and resting-state networks may supply novel avenues for presurgical planning and patient stratification., (Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to assess the sensitivity and specificity of pseudo-continuous arterial spin labeling (PCASL) magnetic resonance angiography (MRA) with 3-dimensional (3D) radial acquisition for the detection of intracranial arteriovenous (AV) shunts., Materials and Methods: A total of 32 patients who underwent PCASL-MRA, clinical magnetic resonance imaging (MRI)/MRA exam, and digital subtraction angiography (DSA) were included in this retrospective analysis. Twelve patients presented with AV shunts. Among these were 8 patients with AV malformations (AVM) and 4 patients with AV fistulas (AVF). The clinical MRI/MRA included 3D time-of-flight MRA in all cases and time-resolved, contrast-enhanced MRA in 9 cases (6 cases with AV shunting). Research MRI and clinical MRI were independently evaluated by 2 neuroradiologists blinded to patient history. A third radiologist evaluated DSA imaging. A diagnostic confidence score was used for the presence of abnormalities associated with AV shunting (1-5). The AVMs were characterized using the Spetzler-Martin scale, whereas AVFs were characterized using the Borden classification. κ Statistics were applied to assess intermodality agreement., Results: Compared with clinical MRA, noncontrast PCASL-MRA with 3D radial acquisition yielded excellent sensitivity and specificity for the detection of intracranial AV shunts (reader 1: 100%/100%, clinical MRA: 91.7%, 94.4%; reader 2: 91.7%/100%, clinical MRA: 91.7%/100%). Diagnostic confidence was 4.8/4.66 with PCASL-MRA and 4.25/4.66 with clinical MRA. For AVM characterization with PCASL-MRA, intermodality agreement with DSA showed κ values of 0.43 and 0.6 for readers 1 and 2, respectively. For AVF characterization, intermodality agreement showed κ values of 0.56 for both readers., Conclusion: Noncontrast PCASL-MRA with 3D radial acquisition is a potential tool for the detection and characterization of intracranial AV shunts with a sensitivity and specificity equivalent or higher than routine clinical MRA.

OBJECTIVE The authors conducted a survey to evaluate differences in the understanding and management of shunt-dependent hydrocephalus among members of the American Society of Pediatric Neurosurgeons (ASPN). METHODS Surveys were sent to all 204 active ASPN members in September 2014. One hundred thirty responses were received, representing a 64% response rate. Respondents were asked 13 multiple-choice and free-response questions regarding 4 fundamental problems encountered in shunted-hydrocephalus management: shunt malfunction, chronic cerebrospinal fluid (CSF) overdrainage, chronic headaches, and slit ventricle syndrome (SVS). RESULTS Respondents agreed that shunt malfunction occurs most often as the result of ventricular catheter obstruction. Despite contrary evidence in the literature, most respondents (66%) also believed that choroid plexus is the tissue most often found in obstructed proximal catheters. However, free-text responses revealed that the respondents' understanding of the underlying pathophysiology of shunt obstruction was highly variable and included growth, migration, or adherence of choroid plexus, CSF debris, catheter position, inflammatory processes, and CSF overdrainage. Most respondents considered chronic CSF overdrainage to be a rare complication of shunting in their practice and reported wide variation in treatment protocols. Moreover, despite a lack of evidence in the literature, most respondents attributed chronic headaches in shunt patients to medical reasons (for example, migraines, tension). Accordingly, most respondents managed headaches with reassurance and/or referral to pain clinics. Lastly, there were variable opinions on the etiology of slit ventricle syndrome (SVS), which included early shunting, chronic overdrainage, and/or loss of brain compliance. Beyond shunt revision, respondents reported divergent SVS treatment preferences. CONCLUSIONS The survey shows that there is wide variability in the understanding and management of shunt-dependent hydrocephalus and its complications. Such discrepancies appear to be derived partly from inconsistent familiarity with existing literature but especially from a paucity of high-quality publications.

Background and Purpose: 4D-DSA is a time-resolved technique that allows viewing of a contrast bolus at any time and from any desired viewing angle. Our hypothesis was that the information content in a 4D-DSA reconstruction was essentially equivalent to that in a combination of 2D acquisitions and a 3D-DSA reconstruction., Materials and Methods: Twenty-six consecutive patients who had both 2D- and 3D-DSA acquisitions were included in the study. The angiography report was used to obtain diagnoses and characteristics of abnormalities. Diagnoses included AVM/AVFs, aneurysms, stenosis, and healthy individuals. 4D-DSA reconstructions were independently reviewed by 3 experienced observers who had no part in the clinical care. Using an electronic evaluation form, these observers recorded their assessments based only on the 4D reconstructions. The clinical evaluations were then compared with the 4D evaluations for diagnosis and lesion characteristics., Results: Results showed both interrater and interclass agreements (κ = 0.813 and 0.858). Comparing the 4D diagnosis with the clinical diagnosis for the 3 observers yielded κ values of 0.906, 0.912, and 0.906. The κ values for agreement among the 3 observers for the type of abnormality were 0.949, 0.845, and 0.895. There was complete agreement on the presence of an abnormality between the clinical and 4D-DSA in 23/26 cases. In 2 cases, there were conflicting opinions., Conclusions: In this study, the information content of 4D-DSA reconstructions was largely equivalent to that of the combined 2D/3D studies. The availability of 4D-DSA should reduce the requirement for 2D-DSA acquisitions., (© 2017 by American Journal of Neuroradiology.)

Inflammation and angiogenesis play major roles in carotid plaque vulnerability. The purpose of this study was to determine whether gray-scale features of carotid plaques are associated with histologic markers for inflammation. Thirty-eight individuals completed a dedicated research carotid ultrasound exam before carotid endarterectomy. Gray-scale analysis was performed on plaque images to measure plaque echogenicity (gray-scale median [GSM] pixel brightness), plaque area, presence of discrete white areas (DWAs) and the percent of black area near the lumen on any one component of the plaque. Plaques with higher ultrasound GSM had greater percent calcification (p = 0.013) on histopathology. Presence of an ultrasound DWA was associated with more plaque hemosiderin (p = 0.0005) and inflammation (p = 0.019) on histopathology examination. The percent of plaque black area in any one component was associated with a higher score for macroscopic ulceration (p = 0.028). Ultrasound plaque characteristics (GSM, DWAs and black areas) represent histopathologic markers associated with plaque vulnerability. ClinicalTrials.gov identifier: NCT02476396., (Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: The angioarchitectural features of an arteriovenous malformation (AVM) provide key information regarding natural history and treatment planning. Because of rapid filling and vascular overlap, two-dimensional (2D) and three-dimensional (3D) digital subtraction angiography (DSA) are often suboptimal for evaluation of these features. We have developed an algorithm that derives a series of fully time-resolved 3D DSA volumes (four-dimensional (4D) DSA) at up to 30 frames/s from a conventional 3D DSA. The temporal/spatial resolution of 4D reconstructions is significantly higher than that provided by current MR angiography and CT angiography techniques. 4D reconstruction allows viewing of an AVM from any angle at any time during its opacification. This feasibility study investigated the potential of 4D DSA to improve the ability to analyze angioarchitectural features compared with conventional 2D and 3D DSA., Methods: 2D, 3D, and 4D DSA reconstructions of angiographic studies of six AVMs were evaluated by three cerebrovascular neurosurgeons and one interventional neuroradiologist. These observers evaluated the ability of each modality to visualize the angioarchitectural features of the AVMs. They also compared the information provided using the combination of 2D and 3D DSA with that provided by a 4D DSA reconstruction., Results: By consensus, 4D DSA provided the best ability to visualize the internal features of the AVM including intranidal aneurysms, fistulae, venous obstructions, and sequence of filling and draining. 2D and 3D images in comparison were limited because of overlap of the vasculature., Conclusions: In this small series, 4D DSA provided better ability to visualize the angioarchitecture of an AVM than conventional methods. Further experience is required to determine the ultimate utility of this technique., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

The role played by vessel disease in stroke-related cognition dysfunction is unclear. We assessed the impact of significant atherosclerotic disease on cognition-even in patients asymptomatic for stroke. We hypothesized that patients would perform poorly relative to controls, but that symptomatic/asymptomatic status (history of stroke/transient ischemic attack) would have no effect. Fifty-two carotid endarterectomy candidates with >60% carotid stenosis and 17 controls underwent a 60-min neuropsychological test protocol. Symptomatic and asymptomatic patients showed deficits in executive function, delayed verbal recall, and general knowledge. Patients symptomatic for stroke also performed worse on tests of language and motor/visuomotor ability. Symptomatic and asymptomatic patients differed in working memory and language task performance. Although all patients showed deficits in executive function and memory, only symptomatic patients showed additional deficits in language and motor function. Cognitive abnormalities in patients viewed as "asymptomatic" for stroke underscore the need for early identification and treatment., (© The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Purpose: 4D DSA allows viewing of 3D DSA as a series of time-resolved volumes of a contrast bolus. There is no comparison of the accuracy of the anatomic information provided by 4D DSA with that available from conventional 2D and 3D DSA. Our purpose was to make this comparison by using a canine model., Materials and Methods: 2D, 3D, and 4D DSA acquisitions were performed in 5 canines from 3 catheter positions in the common carotid artery yielding 15 2D, 15 3D, and 15 4D datasets. For each territory, 3 vascular segments were chosen for comparison. Images were reviewed by 2 experienced neuroradiologists and were graded by the ability to visualize a segment, its filling direction, and preferred technique. Two visualization modes for 4D DSA were compared (volume-rendering technique and MIP)., Results: 4D DSA was preferred in 73.9% of the image sets; 2D, in 22.7%; and 3D, in 3.4%. 4D DSA MIP rendering yielded superior visualization of very small vessel details; the 4D DSA volume-rendering technique offered superior depth and overlap information and better visualization of the surface details of the vasculature., Conclusions: In this study, 4D DSA was preferred over 2D and 3D DSA for analysis of normal vasculature. The ability to provide any view of a vascular territory at any time during passage of a contrast bolus seems likely to reduce the need for many 2D acquisitions during diagnostic and therapeutic procedures. This then potentially translates into a reduction in radiation and contrast dose., (© 2015 by American Journal of Neuroradiology.)

Parasitic infections frequently lead to immune deviation or suppression. However, the application of specific parasitic molecules in regulating autoimmune responses remains to be explored. Here we report on the immune modulatory function of Lacto-N-fucopentaose III (LNFPIII), a schistosome glycan, in an animal model for multiple sclerosis. We found that LNFPIII treatment significantly reduced the severity of experimental autoimmune encephalomyelitis (EAE) and CNS inflammation, and skewed peripheral immune response to a Th2 dominant profile. Inflammatory monocytes (IMCs) purified from LNFPIII-treated mice had increased expression of nitric oxide synthase 2, and mediated T cell suppression. LNFPIII treatment also significantly increased mRNA expression of arginase-1, aldehyde dehydrogenase 1 subfamily A2, indoleamine 2,3-dioxygenase and heme oxygenase 1 in splenic IMCs. Furthermore, LNFPIII treatment significantly reduced trafficking of dendritic cells across brain endothelium in vitro. In summary, our study demonstrates that LNFPIII glycan treatment suppresses EAE by modulating both innate and T cell immune response., (Published by Elsevier Inc.)

CD11b(+)Ly-6C(hi) cells, including inflammatory monocytes (IMCs) and inflammatory dendritic cells (IDCs), are important in infectious, autoimmune, and tumor models. However, their role in T cell regulation is controversial. In this article, we show that T cell regulation by IMCs and IDCs is determined by their activation state and is plastic during an immune response. Nonactivated IMCs and IDCs function as APCs, but activated IMCs and IDCs suppress T cells through NO production. Suppressive IMCs are induced by IFN-γ, GM-CSF, TNF-α, and CD154 derived from activated T cells during their interaction. In experimental autoimmune encephalomyelitis, CD11b(+)Ly-6C(hi) cells in the CNS are increasingly activated from disease onset to peak and switch their function from Ag presentation to T cell suppression. Furthermore, transfer of activated IMCs or IDCs enhances T cell apoptosis in the CNS and suppresses experimental autoimmune encephalomyelitis. These data highlight the interplay between innate and adaptive immunity: immunization leads to the expansion of Ly-6C(hi) myeloid cells initially promoting T cell function. As T cells become highly activated in the target tissue, they induce activation and NO production in Ly-6C(hi) myeloid cells, which in turn suppress T cells and lead to the contraction of local immune response.

The aim of this article was to assess the validity of the emotional and developmental components of the Koppitz human figure drawing test. 2420 children's drawings available in a database resulting from a previous cross sectional study designed to determine the prevalence of neurological diseases in children between 0 and 12 years old in Bogota schools were evaluated. They were scored using the criteria proposed by Koppitz, and classified into 16 groups according to age, gender, and presence/absence of learning or attention problems. The overall results were then compared with the normative study to assess whether descriptive parameters of the two populations were significantly different. There were no significant differences associated with presence/absence of learning and attention disorders or school attended within the overall sample. An Interrater reliability test has been made to assure the homogeneity of scoring by the evaluator team. There were significant differences between this population and that of the original study. New scoring tables contextualized for our population based on the frequency of appearance in this sample are presented. We can conclude that various ethnic, social, and cultural factors can influence the way children draw the human figure. It is thus important to establish local reference values to adequately distinguish between normality and abnormality. The new scoring tables proposed here should be followed up with a clinical study to corroborate their validity.