Cytoneme signaling provides essential contributions to mammalian tissue patterning.

During development, morphogens pattern tissues by instructing cell fate across long distances. Directly visualizing morphogen transport in situ has been inaccessible, so the molecular mechanisms ensuring successful morphogen delivery remain unclear. To tackle this longstanding problem, we developed a mouse model for compromised sonic hedgehog (SHH) morphogen delivery and discovered that endocytic recycling promotes SHH loading into signaling filopodia called cytonemes. We optimized methods to preserve in vivo cytonemes for advanced microscopy and show endogenous SHH localized to cytonemes in developing mouse neural tubes. Depletion of SHH from neural tube cytonemes alters neuronal cell fates and compromises neurodevelopment. Mutation of the filopodial motor myosin 10 (MYO10) reduces cytoneme length and density, which corrupts neuronal signaling activity of both SHH and WNT. Combined, these results demonstrate that cytoneme-based signal transport provides essential contributions to morphogen dispersion during mammalian tissue development and suggest MYO10 is a key regulator of cytoneme function.

Identification and management of low-risk isolated traumatic brain injury patients initially treated at a rural level IV trauma center.

STUDY OBJECTIVE: Our goal was to determine if low-risk, isolated mild traumatic brain injury (TBI) patients who were initially treated at a rural emergency department may have been safely managed without transfer to the tertiary referral trauma center. METHODS: This was a retrospective observational analysis of isolated mild TBI patients who were transferred from a rural Level IV Trauma Center to a regional Level I Trauma Center between 2018 and 2022. Patients were risk-stratified according to the modified Brain Injury Guidelines (mBIG). Data abstracted from the electronic medical record included patient presentation, management, and outcomes. RESULTS: 250 patients with isolated mild TBI were transferred out to the Level I Trauma Center. Fall was the most common mechanism of injury (69.2%). 28 patients (11.2%) were categorized as low-risk (mBIG1). No mBIG1 patients suffered a progression of neurological injury, had worsening of intracranial hemorrhage on repeat head CT, or required neurosurgical intervention. 12/28 (42.9%) of mBIG1 patients had a hospital length of stay of 2 days or less, typically for observation. Those with longer lengths of stay were due to medical complications, such as sepsis, or difficulty in arranging disposition. CONCLUSION: We propose that patients who meet mBIG1 criteria may be safely observed without transfer to a referral Level I Trauma Center. This would be of considerable benefit to patients, who would not need to leave their community, and would improve resource utilization in the region.

Treatment of pediatric intracranial aneurysms: institutional case series and systematic literature review.

INTRODUCTION: Pediatric intracranial aneurysms (IAs) are rare and have distinct clinical profiles compared to adult IAs. They differ in location, size, morphology, presentation, and treatment strategies. We present our experience with pediatric IAs over an 18-year period using surgical and endovascular treatments and review the literature to identify commonalities in epidemiology, treatment, and outcomes. METHODS: We identified all patients < 20 years old who underwent treatment for IAs at our institution between 2005 and 2020. Medical records and imaging were examined for demographic, clinical, and operative data. A systematic review was performed to identify studies reporting primary outcomes of surgical and endovascular treatment of pediatric IAs. Demographic information, aneurysm characteristics, treatment strategies, and outcomes were collected. RESULTS: Thirty-three patients underwent treatment for 37 aneurysms over 18 years. The mean age was 11.4 years, ranging from one month to 19 years. There were 21 males (63.6%) and 12 females (36.4%), yielding a male: female ratio of 1.75:1. Twenty-six (70.3%) aneurysms arose from the anterior circulation and 11 (29.7%) arose from the posterior circulation. Aneurysmal rupture occurred in 19 (57.5%) patients, of which 8 (24.2%) were categorized as Hunt-Hess grades IV or V. Aneurysm recurrence or rerupture occurred in five (15.2%) patients, and 5 patients (15.2%) died due to sequelae of their aneurysms. Twenty-one patients (63.6%) had a good outcome (modified Rankin Scale score 0-2) on last follow up. The systematic literature review yielded 48 studies which included 1,482 total aneurysms (611 with endovascular treatment; 656 treated surgically; 215 treated conservatively). Mean aneurysm recurrence rates in the literature were 12.7% and 3.9% for endovascular and surgical treatment, respectively. CONCLUSIONS: Our study provides data on the natural history and longitudinal outcomes for children treated for IAs at a single institution, in addition to our treatment strategies for various aneurysmal morphologies. Despite the high proportion of patients presenting with rupture, good functional outcomes can be achieved for most patients.

Custom 3D-Printed External Cranial Orthotic for Prevention and Treatment of Syndrome of the Trephined.

Syndrome of the Trephined (SoT) is a frequently misunderstood and underdiagnosed outcome of decompressive craniectomy, especially in cases of trauma. The pressure gradient between atmospheric pressure and the sub-atmospheric intracranial pressure results in a sinking of the scalp overlying the craniectomy site. This gradually compresses the underlying brain parenchyma. This parenchymal compression can disrupt normal autoregulation and subsequent metabolism, yielding symptoms ranging from headaches, dizziness, altered behavior to changes in sensation, and difficulty with ambulation, coordination, and activities of daily living. We present a case of SoT treated with a 3D-printed custom polycarbonate external cranial orthotic that allowed us to re-establish this pressure gradient by returning the cranium to a closed system. The patient demonstrated subjective improvement in quality of life and his symptoms. This was consistent with the re-expanded brain parenchyma on CT imaging.

How do children fare compared with adults? Comparing relative outcomes after thrombectomy for acute ischemic stroke due to large-vessel occlusion.

OBJECTIVE: Safety and efficacy data for endovascular thrombectomy for acute ischemic stroke secondary to large-vessel occlusion in children are lacking compared with those for adults. We undertook an updated systematic review and meta-analysis of endovascular thrombectomy in children and compared their outcomes with adult data. METHODS: We searched PubMed, Medline, and EMBASE databases to identify prospective and retrospective studies describing patients <18 years treated with endovascular thrombectomy for acute ischemic stroke due to large-vessel occlusion. RESULTS: Eight pediatric studies were included (n = 192). Most patients were male (53.1 %), experienced anterior circulation large-vessel occlusion (81.8 %), and underwent endovascular thrombectomy by stent retreiver (70.7 %). The primary outcome was change in National Institutes of Health Stroke Scale score from presentation to 24 h after thrombectomy. Secondary outcomes included modified Rankin scale score improvement and 90-day score, recanalization rates, procedural complications, and mortality rates. After treatment, 88.5% of children had successful recanalization; the mean National Institutes of Health Stroke Scale score reduction was 7.37 (95 % CI 5.11-9.63, p < 0.01). The mean reduction of 6.87 (95 %CI 5.00-8.73, p < 0.01) for adults in 5 clinical trials (n = 634) was similar (Qb = 0.11; p = 0.74). Children experienced higher rates of good neurological outcome (76.1 % vs. 46.0 %, p < 0.01) and revascularization (88.5 % vs. 72.3 %, p < 0.01), fewer major periprocedural complications (3.6 % vs. 30.4 %, p < 0.01), and lower mortality (1.0 % vs. 12.9 %, p < 0.01). CONCLUSIONS: Endovascular thrombectomy may be safe and effective treatment for acute ischemic stroke due to large-vessel occlusion in children. The aggregated data demonstrated high rates of revascularization, favorable long-term neurological outcomes, and low complication rates.

Proton magnetic resonance spectroscopy detects cerebral metabolic derangement in a mouse model of brain coenzyme a deficiency.

BACKGROUND: Pantothenate kinase (PANK) is the first and rate-controlling enzymatic step in the only pathway for cellular coenzyme A (CoA) biosynthesis. PANK-associated neurodegeneration (PKAN), formerly known as Hallervorden-Spatz disease, is a rare, life-threatening neurologic disorder that affects the CNS and arises from mutations in the human PANK2 gene. Pantazines, a class of small molecules containing the pantazine moiety, yield promising therapeutic effects in an animal model of brain CoA deficiency. A reliable technique to identify the neurometabolic effects of PANK dysfunction and to monitor therapeutic responses is needed. METHODS: We applied 1H magnetic resonance spectroscopy as a noninvasive technique to evaluate the therapeutic effects of the newly developed Pantazine BBP-671. RESULTS: 1H MRS reliably quantified changes in cerebral metabolites, including glutamate/glutamine, lactate, and N-acetyl aspartate in a neuronal Pank1 and Pank2 double-knockout (SynCre+ Pank1,2 dKO) mouse model of brain CoA deficiency. The neuronal SynCre+ Pank1,2 dKO mice had distinct decreases in Glx/tCr, NAA/tCr, and lactate/tCr ratios compared to the wildtype matched control mice that increased in response to BBP-671 treatment. CONCLUSIONS: BBP-671 treatment completely restored glutamate/glutamine levels in the brains of the mouse model, suggesting that these metabolites are promising clinically translatable biomarkers for future therapeutic trials.

Arteriovenous malformation surgery in children: the Rady Children's Hospital experience (2002-2019).

PURPOSE: Compared to adult AVMs, there is a paucity of data on the microsurgical treatment of pediatric AVMs. We report our institutional experience with pediatric AVMs treated by microsurgical resection with or without endovascular embolization and radiation therapy. METHODS: We retrospectively reviewed all patients ≤ 18 years of age with cerebral AVMs that underwent microsurgical resection at Rady Children's Hospital 2002-2019. RESULTS: Eighty-nine patients met inclusion criteria. The mean age was 10.3 ± 5.0 years, and 56% of patients were male. In total, 72 (81%) patients presented with rupture. Patients with unruptured AVMs presented with headache (n = 5, 29.4%), seizure (n = 9, 52.9%), or incidental finding (n = 3, 17.7%). The mean presenting mRS was 2.8 ± 1.8. AVM location was lobar in 78%, cerebellar/brainstem in 15%, and deep supratentorial in 8%. Spetzler-Martin grade was I in 28%, II in 45%, III in 20%, IV in 6%, and V in 1%. Preoperative embolization was utilized in 38% of patients and more frequently in unruptured than ruptured AVMs (62% vs. 32%, p = 0.022). Radiographic obliteration was achieved in 76/89 (85.4%) patients. Complications occurred in 7 (8%) patients. Annualized rates of delayed rebleeding and recurrence were 1.2% and 0.9%, respectively. The mean follow-up was 2.8 ± 3.1 years. A good neurological outcome (mRS score ≤ 2) was obtained in 80.9% of patients at last follow-up and was improved relative to presentation for 75% of patients. CONCLUSIONS: Our case series demonstrates high rates of radiographic obliteration and relatively low incidence of neurologic complications of treatment or AVM recurrence.

Surgical management of spontaneous intracerebral hemorrhage: insights from randomized controlled trials.

Spontaneous intracerebral hemorrhages (ICH) are a major cause of neurologic morbidity and mortality. The optimal management strategy of ICH remains controversial. We examine the available randomized controlled trial (RCT) data regarding neurosurgical evacuation of ICHs. A systematic literature review on surgical evacuation of spontaneous ICHs was performed to identify pertinent RCT data published between 1980 and 2019. We identified five RCTs that assessed the clinical impact of evacuation of spontaneous ICHs. Data from two high-quality RCTs randomizing 1033 and 601 patients with spontaneous ICHs (Surgical Trial in Intracerebral Hemorrhage (STICH) I and II) (1) failed to demonstrate a significant clinical benefit of routine open surgical evacuation of spontaneous cortical ICHs and (2) reinforced the high morbidity and mortality associated with ICH. These trials were nonetheless limited by high (> 20%) crossover from the medical to surgical arms. Data from three smaller RCTs on minimally invasive (stereotactic and endoscopic) surgical approaches randomizing 377, 242, and 100 patients with spontaneous ICHs suggest potential benefits relating to mortality and functional outcomes in patients with subcortical ICHs. While these RCTs do not clearly define the role of surgical resection for ICHs, they provide insights into opportunities for patient advocacy, clinical trial design, and future research studies. Ongoing studies building upon the potential for minimally invasive approaches for ICH evacuation may expand the surgical indications for ICH.

Brain Emergency Management Initiative for Optimizing Hub-Helicopter Emergency Medical Systems-Spoke Transfer Networks.

OBJECTIVE: Embolectomy is standard for select occlusions up to 24 hours. Transfer patients may have worse outcomes than those originating in embolectomy centers. We developed the Brain Emergency Management Initiative (BEMI) protocol to streamline this transfer process and mimic the urgency that surrounds ST-elevation myocardial infarction cardiac evaluations. METHODS: We conducted an exploratory assessment of consecutive acute telestroke patients transferred for potential intervention in pre-BEMI versus BEMI periods. Times included spoke in, spoke out, hub in, and groin puncture. Outcomes included discharge destination and symptomatic intracranial hemorrhage. RESULTS: Overall, 68 transfers were assessed. There was a higher National Institute of Neurological Disorders and Stroke in BEMI (11 pre-BEMI vs. 20 B.M., P = .01). There were shorter spoke door in to door out (143 vs. 118 minutes, P = .01) and spoke door out to hub door in times (23 minutes pre-BEMI vs. 21 minutes BEMI, P = .001). For embolectomy patients, there was shorter hub door in to reperfusion (83 minutes pre-BEMI vs. 74 minutes BEMI, P = .04) and recombinant tissue plasminogen decision to groin puncture (155 minutes pre-BEMI vs. 130 minutes BEMI; P = .01). There were no symptomatic intracranial hemorrhage or discharge differences. CONCLUSION: In our hub-helicopter emergency medical services-spoke telestroke network, BEMI led to improved evaluation times. BEMI may serve as a model for future rapid stroke transfer pathways.

Cost-effectiveness of Intraoperative MRI for Treatment of High-Grade Gliomas.

Background Intraoperative MRI has been shown to improve gross-total resection of high-grade glioma. However, to the knowledge of the authors, the cost-effectiveness of intraoperative MRI has not been established. Purpose To construct a clinical decision analysis model for assessing intraoperative MRI in the treatment of high-grade glioma. Materials and Methods An integrated five-state microsimulation model was constructed to follow patients with high-grade glioma. One-hundred-thousand patients treated with intraoperative MRI were compared with 100 000 patients who were treated without intraoperative MRI from initial resection and debulking until death (median age at initial resection, 55 years). After the operation and treatment of complications, patients existed in one of three health states: progression-free survival (PFS), progressive disease, or dead. Patients with recurrence were offered up to two repeated resections. PFS, valuation of health states (utility values), probabilities, and costs were obtained from randomized controlled trials whenever possible. Otherwise, national databases, registries, and nonrandomized trials were used. Uncertainty in model inputs was assessed by using deterministic and probabilistic sensitivity analyses. A health care perspective was used for this analysis. A willingness-to-pay threshold of $100 000 per quality-adjusted life year (QALY) gained was used to determine cost efficacy. Results Intraoperative MRI yielded an incremental benefit of 0.18 QALYs (1.34 QALYs with intraoperative MRI vs 1.16 QALYs without) at an incremental cost of $13 447 ($176 460 with intraoperative MRI vs $163 013 without) in microsimulation modeling, resulting in an incremental cost-effectiveness ratio of $76 442 per QALY. Because of parameter distributions, probabilistic sensitivity analysis demonstrated that intraoperative MRI had a 99.5% chance of cost-effectiveness at a willingness-to-pay threshold of $100 000 per QALY. Conclusion Intraoperative MRI is likely to be a cost-effective modality in the treatment of high-grade glioma. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Bettmann in this issue.

The impact of traveling distance and hospital volume on post-surgical outcomes for patients with glioblastoma.

BACKGROUND: High-volume hospitals are associated with improved outcomes in glioblastoma (GBM). However, the impact of travel burden to high-volume centers is poorly understood. We examined post-operative outcomes between GBM patients that underwent treatment at local, low-volume hospitals with those that traveled long distances to high-volume hospitals. METHODS: The National Cancer Database was queried for GBM patients that underwent surgery (2010-2014). We established two cohorts: patients in the lowest quartile of travel distance and volume (Short-travel/Low-Volume: STLV) and patients in the highest quartile of travel and volume (Long-travel/High-Volume: LTHV). Outcomes analyzed were 30-day, 90-day mortality, overall survival, 30-day readmission, and hospital length of stay. RESULTS: Of 35,529 cases, STLV patients (n = 3414) traveled a median of 3 miles (Interquartile range [IQR] 1.8-4.2) to low-volume centers (5 [3-7] annual cases) and LTHV patients (n = 3808) traveled a median of 62 miles [44.1-111.3] to high-volume centers (48 [42-71]). LTHV patients were younger, had lower Charlson scores, largely received care at academic centers (84.4% vs 11.9%), were less likely to be minorities (8.1% vs 17.1%) or underinsured (6.9% vs 12.1), and were more likely to receive trimodality therapy (75.6% vs 69.2%; all p < 0.001). On adjusted analysis, LTHV predicted improved overall survival (HR 0.87, p = 0.002), decreased 90-day mortality (OR 0.72, p = 0.019), lower 30-day readmission (OR 0.42, p < 0.001), and shorter hospitalizations (RR 0.79, p < 0.001). CONCLUSIONS: Glioblastoma patients who travel farther to high-volume centers have superior post-operative outcomes compared to patients who receive treatment locally at low-volume centers. Strategies that facilitate patient travel to high-volume hospitals may improve outcomes.

Radiation-induced liver injury mimicking liver metastases on FDG-PET-CT after chemoradiotherapy for esophageal cancer : A retrospective study and literature review.

BACKGROUND: For esophageal cancer patients treated with neoadjuvant chemoradiotherapy (nCRT), restaging using F­18-fluorodeoxyglucose (FDG) positron emission tomography computed tomography (PET-CT) following nCRT can detect interval metastases, including liver metastases, in almost 10% of patients. However, in clinical practice, focal FDG liver uptake, unrelated to liver metastases, is observed after chemoradiotherapy. This radiation-induced liver injury (RILI) can potentially lead to overstaging. METHODS: A systematic search for potential cases of RILI after (chemo)radiotherapy for esophageal cancer was performed in the electronic reports from all PET-CT scans made between 2006 and 2015 in our hospital. Additional data about potential cases were obtained from the electronic medical records. A literature review of RILI was also performed. RESULTS: Of 205 patients undergoing nCRT, 6 cases with localized increased FDG uptake in the caudate or left liver lobe following nCRT for esophageal cancer were identified. None of these patients had signs of liver metastases with additional imaging, during surgery, on biopsy, or during follow-up (range 11-46 months). At our institute, the incidence of RILI after neoadjuvant chemoradiotherapy for esophageal cancer was 3%. In the literature, RILI is described in about 8% of patients at the time of restaging. FDG-avid lesions occur in the high radiation dose area, usually corresponding to the caudate or left liver lobe. CONCLUSIONS: FDG accumulation in the caudate or left liver lobe after CRT in the area that received a high radiation dose may be caused by metastases or RILI. Awareness of the pitfall of high FDG uptake in RILI is crucial to avoid misinterpretation and overstaging.

Management of glioblastoma at safety-net hospitals.

BACKGROUND: Safety-net hospitals (SNHs) provide disproportionate care for underserved patients. Prior studies have identified poor outcomes, increased costs, and reduced access to certain complex, elective surgeries at SNHs. However, it is unknown whether similar patterns exist for the management of glioblastoma (GBM). We sought to determine if patients treated at HBHs receive equitable care for GBM, and if safety-net burden status impacts post-treatment survival. METHODS: The National Cancer Database was queried for GBM patients diagnosed between 2010 and 2015. Safety-net burden was defined as the proportion of Medicaid and uninsured patients treated at each hospital, and stratified as low (LBH), medium (MBH), and high-burden (HBH) hospitals. The impact of safety-net burden on the receipt of any treatment, trimodality therapy, gross total resection (GTR), radiation, or chemotherapy was investigated. Secondary outcomes included post-treatment 30-day mortality, 90-day mortality, and overall survival. Univariate and multivariate analyses were utilized. RESULTS: Overall, 40,082 GBM patients at 1202 hospitals (352 LBHs, 553 MBHs, and 297 HBHs) were identified. Patients treated at HBHs were significantly less likely to receive trimodality therapy (OR = 0.75, p < 0.001), GTR (OR = 0.84, p < 0.001), radiation (OR = 0.73, p < 0.001), and chemotherapy (OR = 0.78, p < 0.001) than those treated at LBHs. Patients treated at HBHs had significantly increased 30-day (OR = 1.25, p = 0.031) and 90-day mortality (OR = 1.24, p = 0.001), and reduced overall survival (HR = 1.05, p = 0.039). CONCLUSIONS: GBM patients treated at SNHs are less likely to receive standard-of-care therapies and have increased short- and long-term mortality. Additional research is needed to evaluate barriers to providing equitable care for GBM patients at SNHs.

Markov modeling for the neurosurgeon: a review of the literature and an introduction to cost-effectiveness research.

OBJECTIVE Markov modeling is a clinical research technique that allows competing medical strategies to be mathematically assessed in order to identify the optimal allocation of health care resources. The authors present a review of the recently published neurosurgical literature that employs Markov modeling and provide a conceptual framework with which to evaluate, critique, and apply the findings generated from health economics research. METHODS The PubMed online database was searched to identify neurosurgical literature published from January 2010 to December 2017 that had utilized Markov modeling for neurosurgical cost-effectiveness studies. Included articles were then assessed with regard to year of publication, subspecialty of neurosurgery, decision analytical techniques utilized, and source information for model inputs. RESULTS A total of 55 articles utilizing Markov models were identified across a broad range of neurosurgical subspecialties. Sixty-five percent of the papers were published within the past 3 years alone. The majority of models derived health transition probabilities, health utilities, and cost information from previously published studies or publicly available information. Only 62% of the studies incorporated indirect costs. Ninety-three percent of the studies performed a 1-way or 2-way sensitivity analysis, and 67% performed a probabilistic sensitivity analysis. A review of the conceptual framework of Markov modeling and an explanation of the different terminology and methodology are provided. CONCLUSIONS As neurosurgeons continue to innovate and identify novel treatment strategies for patients, Markov modeling will allow for better characterization of the impact of these interventions on a patient and societal level. The aim of this work is to equip the neurosurgical readership with the tools to better understand, critique, and apply findings produced from cost-effectiveness research.

Impact of preoperative endovascular embolization on immediate meningioma resection outcomes.

OBJECTIVE Preoperative embolization of meningiomas can facilitate their resection when they are difficult to remove. The optimal use and timing of such a procedure remains controversial given the risk of embolization-linked morbidity in select clinical settings. In this work, the authors used a large national database to study the impact of immediate preoperative embolization on the immediate outcomes of meningioma resection. METHODS Meningioma patients who had undergone elective resection were identified in the National (Nationwide) Inpatient Sample (NIS) for the period 2002-2014. Patients who had undergone preoperative embolization were propensity score matched to those who had not, adjusting for patient and hospital characteristics. Associations between preoperative embolization and morbidity, mortality, and nonroutine discharge were investigated. RESULTS Overall, 27,008 admissions met the inclusion criteria, and 633 patients (2.34%) had undergone preoperative embolization and 26,375 (97.66%) had not. The embolization group was younger (55.17 vs 57.69 years, p < 0.001) with a lower proportion of females (63.5% vs 69.1%, p = 0.003), higher Charlson Comorbidity Index (p = 0.002), and higher disease severity (p < 0.001). Propensity score matching retained 413 embolization and 413 nonembolization patients. In the matched cohort, preoperative embolization was associated with increased rates of cerebral edema (25.2% vs 17.7%, p = 0.009), posthemorrhagic anemia or transfusion (21.8% vs 13.8%, p = 0.003), and nonroutine discharge (42.8% vs 35.7%, p = 0.039). There was no difference in mortality (≤ 2.4% vs ≤ 2.4%, p = 0.82). Among the embolization patients, the mean interval from embolization to resection was 1.49 days. On multivariate analysis, a longer interval was significantly associated with nonroutine discharge (OR 1.33, p = 0.004) but not with complications or mortality. CONCLUSIONS Relative to meningioma patients who do not undergo preoperative embolization in the same admission, those who do have higher rates of cerebral edema and nonroutine discharge but not higher rates of stroke or death. Thus, meningiomas requiring preoperative embolization represent a distinct clinical entity that requires prolonged, more complex care. Further, among embolization patients, the timing of resection did not affect the risk of in-hospital complications, suggesting that the timing of surgery can be determined according to surgeon discretion.

The circle of Willis predicts the antihypertensive effects of carotid artery stenting.

OBJECTIVE Carotid artery stenting (CAS) has antihypertensive effects, but the durability and degree of this response remain variable. The authors propose that this clinical variability is a function of the presence or absence of a complete circle of Willis (COW). Incomplete COWs perfuse through a higher-resistance pial collateral pathway, and therefore patients may require a higher mean arterial pressure (MAP). Carotid artery revascularization in these patients would reduce the end-organ collateral demand that has been hypothesized to drive the MAP response. METHODS Using a retrospective, nonrandomized within-subject case-control design, the authors compared the postoperative effects of CAS in patients with and without a complete COW by using changes in MAP and antihypertensive medication as end points. They recorded MAP and antihypertensive medications 3 months prior to surgery, preoperatively, immediately postoperatively, and at the 3-month follow-up. RESULTS Data were collected from 64 consecutive patients undergoing CAS. Patients without a complete COW (25%) were more likely to demonstrate a decrease in BP response to stenting (i.e., a drop in MAP of 10 mm Hg and/or a reduction or cessation of BP medications at 3 months postoperatively). Of the patients in the incomplete COW cohort, 75% had this outcome, whereas of those in the complete COW cohort, only 41% had it (p < 0.041). These findings remained statistically significant in a logistic regression analysis for possible confounders (p < 0.024). A receiver operating curve analysis of preoperative data indicated that a MAP > 96.3 mm Hg was 55.5% sensitive and 57.4% specific for predicting a complete COW and that patients with a MAP > 96.3 mm Hg were more likely to demonstrate a good MAP decrease following CAS (p < 0.0092). CONCLUSIONS CAS is associated with a significant decrease in MAP and/or a reduction/cessation in BP medications in patients in whom a complete COW is absent.

Vessel wall signal enhancement on 3-T MRI in acute stroke patients after stent retriever thrombectomy.

OBJECTIVE In vivo and in vitro studies have demonstrated histological evidence of iatrogenic endothelial injury after stent retriever thrombectomy. However, noncontrast vessel wall (VW)-MRI is insufficient to demonstrate vessel injury. Authors of this study prospectively evaluated iatrogenic endothelial damage after stent retriever thrombectomy in humans by utilizing high-resolution contrast-enhanced VW-MRI. Characterization of VW-MRI changes in vessels subject to mechanical injury from thrombectomy may allow better understanding of the biological effects of this intervention. METHODS The authors prospectively recruited 11 patients for this study. The treatment group included 6 postthrombectomy patients and the control group included 5 subjects undergoing MRI for nonvascular indications. All subjects were evaluated on a Signa HD× 3.0-T MRI scanner with an 8-channel head coil. Both pre- and postcontrast T1-weighted Cube VW images as well as MR angiograms were acquired. Sequences obtained for evaluation of the brain parenchyma included diffusion-weighted, gradient echo, and T2-FLAIR imaging. Two independent neuroradiologists, who were blinded to the treatment status of each patient, determined the presence of VW enhancement. Patient age, National Institutes of Health Stroke Scale score on presentation, location of occlusion, stroke etiology, type of device used, number of device deployments, Thrombolysis in Cerebral Infarction (TICI) reperfusion score, stroke volume, and 90-day modified Rankin Scale score were also noted. RESULTS Postcontrast T1-weighted VW enhancement was detected in the M2 segment in 100% of the thrombectomy patients, in the M1 segment in 83%, and in the internal carotid artery in 50%. One patient also demonstrated A1 segment enhancement, which was attributable to thrombectomy treatment of that vessel segment during the same procedure. None of the control patients demonstrated VW enhancement of their intracranial vasculature on T1-weighted images. CONCLUSIONS The study findings suggest that VW injury incurred during stent retriever thrombectomy can be reliably detected utilizing contrast-enhanced 3-T VW-MRI. The results further demonstrate that endothelial injury is associated with oversizing of stent retrievers relative to the treated vessel. Further studies are needed to evaluate the clinical significance of endothelial injury and to characterize the differential effects of various devices.

Community point distribution of insecticide-treated bed nets and community health worker hang-up visits in rural Zambia: a decision-focused evaluation.

BACKGROUND: In 2013, the Zambian Ministry of Health through its National Malaria Control Programme distributed over two million insecticide-treated bed nets (ITNs) in four provinces using a door-to-door distribution strategy, and more than 6 million ITNs were allocated to be distributed in 2014. This study was commissioned to measure attendance rates at a community point distribution and to examine the impact of follow-up community health worker (CHW) hang-up visits on short and medium-term ITN retention and usage with a view of informing optimal ITN distribution strategy in Zambia. METHODS: Households received ITNs at community point distributions conducted in three rural communities in Rufunsa District, Zambia. Households were then randomly allocated into five groups to receive CHW visits to hang any unhung ITNs at different intervals: 1-3, 5-7, 10-12, 15-17 days, and no hang-up visit. Follow-up surveys were conducted among all households at 7-11 weeks after distribution and at 5-6 months after distribution to measure short- and medium-term household retention and usage of ITNs. RESULTS: Of the 560 pre-registered households, 540 (96.4 %) attended the community point distribution. Self-installation of ITNs by households increased over the first 10 days after the community point distribution. Retention levels remained high over time with 90.2 % of distributed ITNs still in the household at 7-11 weeks and 85.7 % at 5-6 months. Retention did not differ between households that received a CHW visit and those that did not. At 7-11 weeks, households had an average of 73.8 % of sleeping spaces covered compared to 80.3 % at 5-6 months. On average, 65.6 % of distributed ITNs were hanging at 7-11 weeks compared to 63.1 % at 5-6 months. While a CHW hang-up visit was associated with increased usage at 7-11 weeks, this difference was no longer apparent at 5-6 months. CONCLUSIONS: This evaluation revealed that (1) the community point distributions achieved high attendance rates followed by acceptable rates of short-term and medium-term ITN retention and usage, as compared to reported rates achieved by door-to-door distributions in the recent past, (2) CHW hang-up visits had a modest short-term impact on ITN usage but no medium-term effect, and (3) community point distributions can yield sizeable time savings compared to door-to-door distributions.

Characterization of brain development with neuroimaging in a female mouse model of chemotherapy treatment of acute lymphoblastic leukemia.

Background: Survivors of pediatric acute lymphoblastic leukemia (ALL) exhibit abnormal neurocognitive outcomes that are possibly due to exposures to neurotoxic chemotherapy agents. This study aimed to determine the feasibility of characterizing long-term neuroanatomical changes with in vivo neuroimaging in a preclinical model of treatment for ALL. Methods: Female mice (C57BL/6) were randomly assigned to a saline control group (n=10) or a treatment group (n=10) that received intrathecal methotrexate and oral dexamethasone (IT-MTX + DEX). Mice were subsequently scanned three times on a 7T MRI at ages 3, 6, and 12 months (T1, T2, and T3, respectively), which corresponds with human age-equivalents spanning early to late adulthood. Regional brain volumes were automatically segmented, and volume change between timepoints (i.e., T1 to T2; and T2 to T3) were compared between groups (i.e., saline vs. IT-MTX + DEX). Results: Five mice in the IT-MTX + DEX group, and seven mice in the saline group completed all three scans. Between T1 and T2, volumetric change was significantly different between groups in total gray matter [estimate =2.06, 95% confidence interval (CI): 0.27-3.84], the cerebrum (estimate =1.62, 95% CI: 0.14-3.09), claustrum (estimate =0.06, 95% CI: 0.02-0.09), amygdala (estimate =0.16, 95% CI: 0.03-0.29), and striatum (estimate =0.18, 95% CI: 0.01-0.35), with the IT-MTX + DEX group exhibiting a more robust increase in volume than the saline-treated group. Between T2 and T3, group differences in structural brain development were evident for total white matter (estimate =-0.14, 95% CI: -0.27 to -0.01), and the corpus callosum (estimate =-0.09, 95% CI: -0.19 to 0.00) and amygdala (estimate =-0.05, 95% CI: -0.10 to 0.00). In contrast to the rapid brain growth observed earlier in development (i.e., T1 to T2), the IT-MTX + DEX group exhibited an attenuated increase in volume relative to the saline-treated group between T2 and T3. Conclusions: The results demonstrate feasibility of modeling pediatric ALL treatment in a preclinical model and highlight the potential of using preclinical neuroimaging models to gain insight into brain development throughout survivorship.