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Fine and ultra-fine particulate matter (PM) are major constituents of urban air pollution and recognized risk factors for cardiovascular diseases. This review examined the effects of PM exposure on vascular tissue. Specific mechanisms by which PM affects the vasculature include inflammation, oxidative stress, actions on vascular tone and vasomotor responses, as well as atherosclerotic plaque formation. Further, there appears to be a greater PM exposure effect on susceptible individuals with pre-existing cardiovascular conditions.

Background Ventricular shunting is one of the primary modalities for addressing hydrocephalus in both children and adults. Despite advances in shunt technology and surgical practices, shunt failure is a persistent challenge for neurosurgeons, and shunt revisions account for a substantial proportion of all shunt-related procedures. There are a wealth of studies elucidating failure patterns and patient demographics in pediatric cohorts; however, data in adults are less uniform. We sought to determine the rates of all-cause and shunt failure readmission in adults who underwent the insertion of a ventricular shunt. Methods We queried the Nationwide Readmissions Database from 2010 to 2014 to evaluate new ventricular shunts placed in adults with hydrocephalus. We sought to determine the rates of all-cause and shunt revision-related readmissions and to characterize factors associated with readmissions. We analyzed predictors including patient demographics, hospital characteristics, shunt type, and hydrocephalus cause. Results Analysis included 24,492 initial admissions for shunt placement in patients with hydrocephalus. Of patients, 9.17% required a shunt revision within the first 6 months; half of all revisions occurred within the first 41 days. There were 4044 (16.50%) 30-day and 5758 (28.8%) 90-day all-cause readmissions. In multivariable analysis, patients with a ventriculopleural shunt, Medicare insurance, and younger age had increased likelihood for shunt revision. Notable predictors for all-cause readmission were insurance type, length of hospitalization, age, comorbidities, and hydrocephalus cause. Conclusions Most shunt revisions occurred during the first 2 months. Readmissions occurred frequently. We identified patient factors that were associated with all-cause and shunt failure readmissions.

BackgroundStroke systems of care employ a hub-and-spoke model, with fewer centers performing mechanical thrombectomy (MT) compared with stroke-receiving centers, where a higher number offer high-level, centralized treatment to a large number of patients.ObjectiveTo characterize rates and outcomes of readmission to index and non-index hospitals for patients with ischemic stroke who underwent MT.MethodsThis study leveraged a population-based, nationally representative sample of patients with stroke undergoing MT from the Nationwide Readmissions Database between 2010 and 2014. Descriptive, logistic regression analyses, and univariate and multivariate logistic regression models were carried out to determine patient- and hospital-level factors, mortality, complications, and subsequent readmissions associated with index and non-index hospitals' 90-day readmissions.ResultsIn the study, 2111 patients with a stroke were treated with MT, of whom 534 were readmitted within 90 days. The most common reasons for readmission were: septicemia (5.9%), atrial fibrillation (4.8%), and cerebral artery occlusion with infarct (4.8%). Among readmitted patients, 387 (74%) were readmitted to index and 136 (26%) to non-index hospitals. On multivariable logistic regression analysis, non-index hospital readmission was not independently associated with major complications (p=0.09), mortality (p=0.34), neurological complications (p=0.47), or second readmission (p=0.92).ConclusionOne-quarter of patients with a stroke treated with MT were readmitted within 90 days, and one quarter of these patients were readmitted to non-index hospitals. Readmission to a non-index hospital was not associated with mortality or increased complication rates. In a hub-and-spoke model it is important that follow-up care for a specialized procedure can be performed effectively at a vast number of non-index hospitals covering a large geographic area.

STUDY DESIGN Retrospective analysis of a prospective registry. OBJECTIVE We utilized the Quality Outcomes Database (QOD) registry to investigate the "July Effect" at QOD spondylolisthesis module sites with residency trainees. SUMMARY OF BACKGROUND DATA There is a paucity of investigation on the long-term outcomes following surgeries involving new trainees utilizing high-quality, prospectively collected data. METHODS This was an analysis of 608 patients who underwent single-segment surgery for grade 1 degenerative lumbar spondylolisthesis at 12 high-enrolling sites. Surgeries were classified as occurring in July or not in July (non-July). Outcomes collected included estimated blood loss, length of stay, operative time, discharge disposition, complications, reoperation and readmission rates, and patient-reported outcomes (Oswestry Disability Index [ODI], Numeric Rating Scale [NRS] Back Pain, NRS Leg Pain, EuroQol-5D [EQ-5D] and the North American Spine Society [NASS] Satisfaction Questionnaire). Propensity score-matched analyses were utilized to compare postoperative outcomes and complication rates between the July and non-July groups. RESULTS Three hundred seventy-one surgeries occurred at centers with a residency training program with 21 (5.7%) taking place in July. In propensity score-matched analyses, July surgeries were associated with longer operative times ( average treatment effect = 22.4 minutes longer, 95% confidence interval 0.9-449.0, P = 0.041). Otherwise, July surgeries were not associated with significantly different outcomes for the remaining perioperative parameters (estimated blood loss, length of stay, discharge disposition, postoperative complications), overall reoperation rates, 3-month readmission rates, and 24-month ODI, NRS back pain, NRS leg pain, EQ-5D, and NASS satisfaction score (P > 0.05, all comparisons). CONCLUSION Although July surgeries were associated with longer operative times, there were no associations with other clinical outcomes compared to non-July surgeries following lumbar spondylolisthesis surgery. These findings may be due to the increased attending supervision and intraoperative education during the beginning of the academic year. There is no evidence that the influx of new trainees in July significantly affects long-term patient-centered outcomes.Level of Evidence: 3.

National and regional systems of stroke care are designed to provide patients with widespread access to hospitals with thrombolytic capabilities. However, such triaging systems may contribute to fragmentation of care. This study aims to compare rates of readmission and outcomes between index and non-index hospitals for stroke patients following intravenous thrombolytic therapy (IVT). This study utilized a nationally representative sample of stroke patients with IVT from the Nationwide Readmissions Database from 2010 to 2014. Descriptive and regression analyses were performed for patient and hospital level factors that influenced 90-day readmissions and regression models were used to identify differences in mortality, complications, and repeat readmissions between patients readmitted to index (facility where IVT was administered) and non-index hospitals. In the study, 49415 stroke patients were treated with IVT, of whom 21.7% were readmitted within 90 days. Among readmissions, 79.4% of patients were readmitted to index hospitals and 20.6% to non-index hospitals. On multivariate logistic regression analysis, index hospital readmission was independently associated with lower frequency of second readmissions (non-index OR 1.09, 95%CI 1.07-1.11, p

Author(s): Winkler, Ethan A; Lu, Alex; Morshed, Ramin A; Yue, John K; Rutledge, W Caleb; Burkhardt, Jan-Karl; Patel, Arati B; Ammanuel, Simon G; Braunstein, Steve; Fox, Christine K; Fullerton, Heather J; Kim, Helen; Cooke, Daniel; Hetts, Steven W; Lawton, Michael T; Abla, Adib A; Gupta, Nalin | Abstract: OBJECTIVE:Brain arteriovenous malformations (AVMs) consist of dysplastic blood vessels with direct arteriovenous shunts that can hemorrhage spontaneously. In children, a higher lifetime hemorrhage risk must be balanced with treatment-related morbidity. The authors describe a collaborative, multimodal strategy resulting in effective and safe treatment of pediatric AVMs. METHODS:A retrospective analysis of a prospectively maintained database was performed in children with treated and nontreated pediatric AVMs at the University of California, San Francisco, from 1998 to 2017. Inclusion criteria were age ≤ 18 years at time of diagnosis and an AVM confirmed by a catheter angiogram. RESULTS:The authors evaluated 189 pediatric patients with AVMs over the study period, including 119 ruptured (63%) and 70 unruptured (37%) AVMs. The mean age at diagnosis was 11.6 ± 4.3 years. With respect to Spetzler-Martin (SM) grade, there were 38 (20.1%) grade I, 40 (21.2%) grade II, 62 (32.8%) grade III, 40 (21.2%) grade IV, and 9 (4.8%) grade V lesions. Six patients were managed conservatively, and 183 patients underwent treatment, including 120 resections, 82 stereotactic radiosurgery (SRS), and 37 endovascular embolizations. Forty-four of 49 (89.8%) high-grade AVMs (SM grade IV or V) were treated. Multiple treatment modalities were used in 29.5% of low-grade and 27.3% of high-grade AVMs. Complete angiographic obliteration was obtained in 73.4% of low-grade lesions (SM grade I-III) and in 45.2% of high-grade lesions. A periprocedural stroke occurred in a single patient (0.5%), and there was 1 treatment-related death. The mean clinical follow-up for the cohort was 4.1 ± 4.6 years, and 96.6% and 84.3% of patients neurologically improved or remained unchanged in the ruptured and unruptured AVM groups following treatment, respectively. There were 16 bleeding events following initiation of AVM treatment (annual rate: 0.02 events per person-year). CONCLUSIONS:Coordinated multidisciplinary evaluation and individualized planning can result in safe and effective treatment of children with AVMs. In particular, it is possible to treat the majority of high-grade AVMs with an acceptable safety profile. Judicious use of multimodality therapy should be limited to appropriately selected patients after thorough team-based discussions to avoid additive morbidity. Future multicenter studies are required to better design predictive models to aid with patient selection for multimodal pediatric care, especially with high-grade AVMs.

INTRODUCTION: Successful endovascular management of aneurysmal subarachnoid hemorrhage (aSAH) requires timely access to significant resources. Prior studies suggest an association between time to treatment and patient outcome. Patients treated at safety- net hospitals are thought to be particularly vulnerable to disparities in access to interventions that require substantial technological resources. We hypothesize that patients treated at safety-net hospitals are at greater risk for delayed access to endovascular treatment. MATERIALS AND METHODS: Adults undergoing endovascular coiling procedures between 2002–2011 in the Nationwide Inpatient Sample were included. Hospitals in the quartile with the highest proportion of Medicaid or uninsured patients were defined as safety-net hospitals. A multivariable model including patient and hospital-level factors was constructed to permit analysis of delays in endovascular treatment (defined as time to treatment greater than 3 days). RESULTS: Analysis included 7,109 discharges of patients with aSAH undergoing endovascular coil embolization procedures from 2002–2011. The median time to coil embolization in all patients was 1 day; 10.1% of patients waited more than three days until treatment. In multivariable analysis, patients treated at safety-net hospitals were more likely to have a prolonged time to coil embolization (OR 1.32, p

Clinical outcomes in the surgical management of severe traumatic brain injury (TBI) have been shown to vary across different hospital institutions. The effect of the safety-net burden on postoperative mortality, complication rates, and failure to rescue rates is unclear. We evaluated the relationship of the safety-net burden with outcomes in the treatment of patients with severe TBI undergoing neurosurgery.The hospitals were grouped according to their safety-net burden, defined as the proportion of Medicaid and uninsured patient charges for all hospitalizations during that time. Multivariate analyses were performed to examine significant associations with the degree of safety-net burden while controlling for potential confounders.Data from 20,989 encounters in 788 hospitals were included. Compared with low-burden hospitals (LBHs), high-burden hospitals (HBHs; odds ratio [OR], 1.48; 95% confidence interval [CI], 1.04-2.12; P = 0.03) had greater mortality rates. Major complications were more likely to occur at HBHs (OR, 1.44; 95% CI, 1.12-1.84; P0.01) compared with LBHs. The failure to rescue rates were similar among all safety-net burden hospital groups. Patients at HBHs also had an increased likelihood of an extended length of stay (OR, 1.92; 95% CI, 1.12-3.29; P = 0.02) and receiving a tracheostomy or gastrostomy (OR, 1.99; 95% CI, 1.36-2.89; P0.01) compared with patients at LBHs.The present study found that a greater hospital safety-net burden was independently associated with greater rates of mortality and major complications in the treatment of patients with severe TBI undergoing neurosurgery. Further research in evaluating the cause of disparities in mortality outcomes at high safety-burden hospitals is needed.

Inpatient hospital stays for patients with epilepsy represent a significant burden on patients and society. Identifying factors that contribute to such costs aides in developing effective strategies to address this burden. July admissions have been associated with higher rates of complications and worse outcomes, attributed to the presence of new physicians. This study aims to evaluate whether epilepsy patients admitted in July have higher preventable complication rates and mortality than during the rest of the year.Data was derived from the Nationwide Inpatient Sample (NIS) for epilepsy admissions for the years 2000-2010. Multivariable analyses assessed the effect of July against non-July admission on "hospital acquired complications" (HAC), which are complications identified as owing to preventable causes and mortality. Additionally, the total adjusted charges and prolonged length of stay (pLOS) for July admissions were compared to the 50th percentile.A total of 12,997,181 admissions for epilepsy were identified with 993,619 (8%) occurring in July, 10,810,900 (83%) were non-July months, and 1,192,662 (9%) were missing data. Patients admitted in July showed an increased association for HAC events (RR=1.02, [1.01,1.03], p0.01), but a decrease in mortality (RR=0.96, [0.95,0.97], p0.01). There was no difference in rates of higher total adjusted charges for July admissions (RR=1.00, [1.00,1.00], p0.01) and a decrease in rates of pLOS (RR=0.99, [0.98,0.99], p0.01).In the epilepsy population, although July admissions were associated with a slight increase in HAC events, there was a non-significant or decreased rate of mortality, LOS, and total charge. Our results suggest that although complications were increased in July, possibly due to new staff, supervision is sufficient to prevent significant burden on patients and hospitals.

The purpose of this review is to describe recent clinical and epidemiological studies examining the adverse effects of urban air pollution on the central nervous system (CNS). Air pollution and particulate matter (PM) are associated with neuroinflammation and reactive oxygen species (ROS). These processes affect multiple CNS pathways. The conceptual framework of this review focuses on adverse effects of air pollution with respect to neurocognition, white matter disease, stroke, and carotid artery disease. Both children and older individuals exposed to air pollution exhibit signs of cognitive dysfunction. However, evidence on middle-aged cohorts is lacking. White matter injury secondary to air pollution exposure is a putative mechanism for neurocognitive decline. Air pollution is associated with exacerbations of neurodegenerative conditions such as Alzheimer’s and Parkinson’s Diseases. Increases in stroke incidences and mortalities are seen in the setting of air pollution exposure and CNS pathology is robust. Large populations living in highly polluted environments are at risk. This review aims to outline current knowledge of air pollution exposure effects on neurological health.

Chronic cerebral hypoperfusion (CCH) can result in vascular dementia and small vessel white matter ischemic injury. These findings have previously been demonstrated in a murine experimental model of CCH secondary to bilateral common carotid artery stenosis (BCAS). This study sought to elucidate the effects of CCH on recognition memory as assessed by the novel object recognition (NOR) test and histological analysis of the hippocampus and perirhinal cortex.Studies were performed on ten-week-old male mice using bilateral 0.18 mm microcoils to narrow the carotid arteries in accordance with prior publications. Following surgery, BCAS (n = 6) and sham (n = 6) mice were evaluated using NOR and 8-arm radial maze testing paradigms. Tissue damage was assessed using HE staining on a parallel cohort of mice (n = 6 BCAS, n = 7 sham).In the NOR paradigm, BCAS mice demonstrated significant deficits in short-term memory. Consistent with prior studies, BCAS mice also performed significantly worse on 8-arm radial maze testing. BCAS mice exhibited significantly more neuronal injury in the perirhinal cortex when compared to sham-operated mice. However, no significant differences in neuronal damage were observed in the CA1 region of the hippocampus.Experimental CCH secondary to BCAS results in recognition memory deficits on NOR testing. Damage to the perirhinal cortex, rather than to the hippocampus, may underlie this impairment.

Intracerebral hemorrhage and, more specifically, intraparenchymal hemorrhage, are devastating disease processes with poor clinical outcomes. Primary injury to the brain results from initial hematoma expansion while secondary hemorrhagic injury occurs from blood-derived products such as hemoglobin, heme, iron, and coagulation factors that overwhelm the brains natural defenses. Novel neuroprotective treatments have emerged that target primary and secondary mechanisms of injury. Nonetheless, translational application of neuroprotectants from preclinical to clinical studies has yet to show beneficial clinical outcomes. This review summarizes therapeutic agents and neuroprotectants in ongoing clinical trials aimed at targeting primary and secondary mechanisms of injury after intraparenchymal hemorrhage.

Background Venous thromboembolism (VTE) is responsible for many hospital readmissions each year, particularly among postsurgical cohorts. Because early and indiscriminate VTE prophylaxis carries catastrophic consequences in postcraniotomy cohorts, identifying factors associated with a high risk for thromboembolic complications is important for guiding postoperative management. Objective To determine VTE incidence in patients undergoing nonemergent craniotomy and to evaluate for factors that predict 30-day and 90-day readmission with VTE. Methods The 2010–2014 cohorts of the Nationwide Readmissions Database were used to generate a large heterogeneous craniotomy sample. Results There were 89,450 nonemergent craniotomies that met inclusion criteria. Within 30 days, 1513 patients (1.69%) were readmitted with VTE diagnoses; among them, 678 (44.8%) had a diagnosis of deep vein thrombosis alone, 450 (29.7%) had pulmonary embolism alone, and 385 (25.4%) had both. The corresponding 30-day deep vein thrombosis and pulmonary embolism incidences were 1.19% and 0.93%, respectively. In multivariate analysis, several factors were significantly associated with VTE readmission, namely, craniotomy for tumor, corticosteroids, advanced age, greater length of stay, and discharge to institutional care. Conclusions Craniotomies for tumor, corticosteroids, advanced age, prolonged length of stay, and discharge to institutional care are significant predictors of VTE readmission. The implication of steroids, coupled with their ubiquity in neurosurgery, makes them a potentially modifiable risk factor and a prime target for VTE reduction in craniotomy cohorts. Furthermore, the fact that dose is proportional to VTE risk in the literature suggests that careful consideration should be given toward decreasing regimens in situations in which use of a lower dose might prove equally sufficient.

Objective Surgical site infections (SSIs) carry significant patient morbidity and mortality and are a major source of readmissions after craniotomy. Because of their deleterious effects on health care outcomes and costs, identifying modifiable risk factors holds tremendous value. However, because SSIs after craniotomy are rare and most existing data comprise single-institution studies with small sample sizes, many are likely underpowered to discern for such factors. The objective of this study was to use a large hetereogenous patient sample to determine SSI incidence after nonemergent craniotomy and identify factors associated with readmission and subsequent need for wound washout. Methods We used the 2010–2014 Nationwide Readmissions Database cohorts to discern for factors predictive of SSI and washout. Results We identified 93,920 nonemergent craniotomies. There were 2079 cases of SSI (2.2%) and 835 reoperations for washout (0.89%) within 30 days of index admission and there were 2761 cases of SSI (3.6%) and 1220 reoperations for washout (1.58%) within 90 days. Several factors were predictive of SSI in multivariate analysis, including tumor operations, external ventricular drain (EVD), age, length of stay, diabetes, discharge to an intermediate-care facility, insurance type, and hospital bed size. Many of these factors were similarly implicated in reoperation for washout. Conclusions SSI incidence in neurosurgery is low and most readmissions occur within 30 days. Several factors predicted SSI after craniotomy, including operations for tumor, younger age, hospitalization length, diabetes, discharge to institutional care, larger hospital bed size, Medicaid insurance, and presence of an EVD. Diabetes and EVD placement may represent modifiable factors that could be explored in subsequent prospective studies for their associations with cranial SSIs.

Background and Purpose Estradiol is a sex steroid hormone known to protect the brain against damage related to transient and global cerebral ischemia. In the present study, we leverage an experimental murine model of bilateral carotid artery stenosis (BCAS) to examine the putative effects of estradiol therapy on chronic cerebral hypoperfusion. We hypothesize that long-term estradiol therapy protects against white matter injury and declarative memory deficits associated with chronic cerebral hypoperfusion. Methods Adult male C57BL/6J mice underwent either surgical BCAS or sham procedures. Two days after surgery, the mice were given oral estradiol (Sham+E, BCAS+E) or placebo (Sham+P, BCAS+P) treatments daily for 31-34 days. All mice underwent Novel Object Recognition (NOR) testing 31-34 days after the start of oral treatments. Following sacrifice, blood was collected and brains fixed, sliced, and prepared for histological examination of white matter injury and extracellular signal-regulated kinase (ERK) expression. Results Animals receiving long-term oral estradiol therapy (BCAS-E2 and Sham-E2) had higher plasma estradiol levels than those receiving placebo treatment (BCAS-P and Sham-P). BCAS-E2 mice demonstrated less white matter injury (Kluver–Barrera staining) and performed better on the NOR task compared to BCAS-P mice. ERK expression in the brain was increased in the BCAS compared to sham cohorts. Among the BCAS mice, the BCAS-E2 cohort had a greater number of ERK + cells. Conclusion This study demonstrates a potentially protective role for oral estradiol therapy in the setting of white matter injury and declarative memory deficits secondary to murine chronic cerebral hypoperfusion.

Epidemiological studies have established an association between air pollution particulate matter exposure (PM2.5) and neurocognitive decline. Experimental data suggest that microglia play an essential role in air pollution PM-induced neuroinflammation and oxidative stress. This study examined the effect of nano-sized particulate matter (nPM) on complement C5 deposition and microglial activation in the corpus callosum of mice (C57BL/6J males). nPM was collected in an urban Los Angeles region impacted by traffic emissions. Mice were exposed to 10 weeks of re-aerosolized nPM or filtered air for a cumulative 150 hours. nPM-exposed mice exhibited reactive microglia and 2-fold increased local deposition of complement C5/ C5α proteins and complement component C5a receptor 1 (CD88) in the corpus callosum. However, serum C5 levels did not differ between nPM and filtered air cohorts. These findings demonstrate white matter C5 deposition and microglial activation secondary to nPM exposure. The C5 upregulation appears to be localized to the brain.

Murine chronic cerebral hypoperfusion (CCH) results in white matter (WM) injury and behavioral deficits. Pericytes influence blood–brain barrier (BBB) integrity and cerebral blood flow. Under hypoxic conditions, pericytes detach from perivascular locations increasing vessel permeability and neuronal injury. This study characterizes the time course of BBB dysfunction and pericyte coverage following murine experimental CCH secondary to bilateral carotid artery stenosis (BCAS). Mice underwent BCAS or sham operation. On post-procedure days 1, 3, 7 and 30, corpus callosum BBB permeability was characterized using Evans blue (EB) extravasation and IgG staining and pericyte coverage/count was calculated. The BCAS cohort demonstrated increased EB extravasation on postoperative days 1 ( p = 0.003) 3 ( p = 0.002), and 7 ( p = 0.001) when compared to sham mice. Further, EB extravasation was significantly greater ( p = 0.05) at day 3 than at day 30 in BCAS mice. BCAS mice demonstrated a nadir in pericyte coverage and count on post-operative day 3 ( p

Background Overshunting of cerebrospinal fluid may lead to intracranial hypotension and dilation of spinal epidural veins. Radiculopathy may rarely occur secondary to engorged spinal epidural veins. In addition, the cause of radiculopathy may be obscured by concomitant spinal degenerative changes. We present a case and review the pathogenesis as well as the current clinical literature. Case Description A 29-year-old woman presented with positional headaches from intracranial hypotension in the setting of cerebrospinal fluid overshunting. The patient also had back pain and lumbar radiculopathy, which became more severe after lumboperitoneal shunt placement. On radiographic work-up, there was evidence of right L5 nerve root impingement secondary to a disc bulge and an engorged lumbar epidural venous plexus secondary to overshunting. The patient underwent surgery for a planned L4-5 decompression with a transforaminal lumbar interbody fusion. The operation was complicated by rapid blood loss originating from the epidural venous plexus, and we were unable to safely place the interbody graft. Conclusions Spinal surgeons need to be aware of the rare diagnosis of radiculopathy secondary to epidural venous plexus engorgement, as it may change the treatment approach or lead to deleterious intraoperative consequences, such as hemorrhage.

Background Individuals with 22q11.2 microdeletion syndrome (22q11DS) have elevated rates of autism spectrum disorder (ASD), although the diagnosis is controversial. To determine whether there is a biological substrate of ASD in patients with 22q11DS, we examined neurocognitive and structural neuroanatomic differences between those with 22q11DS and an ASD diagnosis (22q11DS-ASD + ) and those with 22q11DS without ASD (22q11DS-ASD − ). We then determined whether these differences were better characterized within a categorical or dimensional framework. Methods We collected multiple neurocognitive measures and high-resolution T1-weighted magnetic resonance imaging scans from 116 individuals (29 patients who were 22q11DS-ASD + , 32 patients who were 22q11DS-ASD − , and 55 typically developing controls) who were between 6 and 26 years of age. Measures of subcortical volume, cortical thickness (CT), and surface area were extracted using the FreeSurfer image analysis software. Group differences in neurocognitive and neuroanatomic measures were assessed; regression analyses were then performed to determine whether a categorical or dimensional measure of ASD was a better predictor of neurocognitive impairment or neuroanatomic abnormalities observed in patients with 22q11DS-ASD + . Results In comparison to 22q11DS-ASD – individuals, 22q11DS-ASD + participants had decreased bilateral parahippocampal CT and decreased right amygdala volumes. Those with 22q11DS-ASD + also showed slowed processing speed and impairments in visuospatial and facial memory. Neurocognitive impairments fit a dimensional model of ASD, whereas reductions in parahippocampal CT were best explained by a categorical measure of ASD. Conclusions A combination of categorical and dimensional measures of ASD may provide the most comprehensive understanding of ASDs in individuals with 22q11DS.

Introduction 22q11.2 deletion syndrome (22q11DS) represents one of the largest known genetic risk factors for psychosis, yet the neurobiological mechanisms underlying symptom development are not well understood. Here we conducted a cross-sectional study of 22q11DS to decompose cortical volume into its constituent parts, cortical thickness (CT) and surface area (SA), which are believed to have distinct neurodevelopmental origins. Methods High-resolution T1-weighted scans were collected on 65 participants (31 22q11DS, 34 demographically comparable typically developing controls, 10–25 years old). Measures of cortical volume, CT, and SA were extracted from regions of interest using the FreeSurfer image analysis suite. Group differences and age-related trajectories in these structures, as well as their association with psychotic symptomatology, were assessed. Results Relative to controls, 22q11DS participants showed bilateral volumetric reductions in the inferior temporal cortex, fusiform gyrus, anterior cingulate, superior parietal cortex, and cuneus, which were driven by decreased SA in these regions. 22q11DS participants also had increased volumes, driven by increased CT, in bilateral insula regions. 22q11DS youth had increased CT in frontal regions, particularly middle frontal and medial orbitofrontal cortices. A pattern of age-associated cortical thinning was observed in typically developing controls in brain regions associated with visual and sensory information-processing (i.e., left pericalcarine cortex and fusiform gyrus, right lingual and postcentral cortices). However, this relationship was disrupted in 22q11DS participants. Finally, correlational analyses revealed that increased CT in right medial orbitofrontal cortex was associated with increased positive symptom severity in 22q11DS. Conclusion Differential disruptions of CT and SA in distinct cortical regions in 22q11DS may indicate abnormalities in distinct developmental neural processes. Further, neuroanatomic abnormalities in medial frontal brain structures disproportionately affected in idiopathic schizophrenia were associated with psychotic symptom severity in 22q11DS youth, suggesting that disrupted biological processes in these cortical regions may underlie development of psychotic symptoms, both in 22q11DS and in the broader population., Highlights • 22q11DS offers a valuable model for neurobiological mechanisms of psychosis. • First study of multiple structural MRI indices in 22q11DS. • Reduced surface area in multiple neuroanatomic regions in 22q11DS. • Increased cortical thickness in multiple frontal regions and insula in 22q11DS. • Orbitofrontal abnormalities associated with positive symptom severity in 22q11DS.

This study examines the effects of nano-size particulate matter (nPM) exposure in the setting of murine reperfused stroke. Particulate matter is a potent source of inflammation and oxidative stress. These processes are known to influence stroke progression through recruitment of marginally viable penumbral tissue into the ischemic core. nPM was collected in an urban area in central Los Angeles, impacted primarily by traffic emissions. Re-aerosolized nPM or filtered air was then administered to mice through whole body exposure chambers for forty-five cumulative hours. Exposed mice then underwent middle cerebral artery occlusion/ reperfusion. Following cerebral ischemia/ reperfusion, mice exposed to nPM exhibited significantly larger infarct volumes and less favorable neurological deficit scores when compared to mice exposed to filtered air. Mice exposed to nPM also demonstrated increases in markers of inflammation and oxidative stress in the region of the ischemic core. The findings suggest a detrimental effect of urban airborne particulate matter exposure in the setting of acute ischemic stroke.