Search

OBJECTIVE Neurosurgical outcomes are not well defined in the management of pediatric patients with cerebral venous sinus thrombosis (CVST) following acute mastoiditis. Specific notable sequelae are otogenic (otitic) hydrocephalus and CVST management. Correspondingly, the aim of this study was to integrate the currently published metadata to summarize these outcomes. METHODS Electronic searches were performed using the Ovid Embase, PubMed, Scopus, and Cochrane databases from inception to November 2022 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Cohort-level data were then abstracted for analysis for appropriate pediatric patients. Outcomes were pooled by random-effects meta-analyses of proportions where possible. RESULTS Twenty-three study cohorts describing 312 pediatric patients with otogenic CVST were included. At a cohort level, the median patient age was 6 years among 181 boys (58%) and 131 girls (42%). Modeling indicated papilledema at presentation in 46% of cases (95% CI 30%–62%). Regarding management, antibiotics were applied universally in all cases, mastoidectomy or other otologic surgery was performed in 91% (95% CI 82%–98%), and prophylactic anticoagulation was administered in 86% (95% CI 75%–95%). There was only 1 case (0.3%) of postprocedural intracranial hemorrhage, and there were no deaths reported among all studies. Although diagnostic lumbar puncture was performed in 14% (95% CI 3%–28%) at presentation, clinical otogenic hydrocephalus was ultimately suspected in 31% (95% CI 14%–49%), and acetazolamide was given in 65% (95% CI 35%–91%) overall. There were 10 cases (3%) that proceeded to permanent CSF diversion in the form of ventricular shunting. At a median follow-up of 8 months among all studies, the venous sinus was completely recanalized in 67% (95% CI 53%–79%). CONCLUSIONS Most CVSTs following acute mastoiditis will recanalize with the standard use of antibiotics, otologic surgery, and anticoagulation, with minimal symptomatic hemorrhage risk. However, an appreciable proportion of these patients will develop symptomatic otogenic hydrocephalus, and it is imperative that the appropriate surveillance and workup is performed to fully optimize patient outcomes long-term. The possible need for permanent CSF diversion should be recognized.

OBJECTIVE Morning glory disc anomaly (MGDA), a congenital abnormality of the optic nerve, may be associated with moyamoya arteriopathy, a cerebrovascular abnormality. In this study, the authors aimed to define the temporal evolution of cerebrovascular arteriopathy in patients with MGDA to characterize a rational strategy for screening and management over time. METHODS The records of pediatric neurosurgical patients at two academic institutions were retrospectively reviewed to identify cases of cerebral arteriopathy and MGDA, including radiographic and clinical records documenting patient outcomes of medical and surgical management. RESULTS Thirteen cases of moyamoya syndrome (MMS) associated with MGDA were identified in 13 children aged 0.6–17 years. The pattern of arteriopathy resembled that of non-MGDA MMS, with predominantly anterior circulation involvement. The arteriopathy lateralized with the MGDA, although 3 patients also had contralateral involvement. The overall group was followed for a median of 3.2 years. Radiological biomarkers of cerebral ischemia were applied to guide surgical decisions, and more than half of the patients (7 of 13) had evidence of stroke or progression on serial imaging. Nine patients underwent revascularization surgery, and 4 were managed medically. CONCLUSIONS Cerebral arteriopathy observed in association with MGDA resembles MMS seen in patients without MGDA and is dynamic, with progression observed over months to years and an associated risk of cerebral ischemia that indicates a role for surgical revascularization. Radiological biomarkers may augment clinical data to identify candidates for revascularization surgery.

OBJECTIVE The assessment of hemorrhagic risk is of central importance in the management of pediatric brain arteriovenous malformations (AVMs). A recently published scoring system, the R2eD AVM (race, exclusive deep location or not, AVM size < 3 or ≥ 3, venous drainage exclusively deep or not, and monoarterial feeding or >1 arterial feeders) considers patient race and AVM location, size, venous drainage, and arterial supply and was successfully externally validated for use in adults to predict the risk of AVM hemorrhagic presentation. In this study the authors sought to externally validate the R2eD AVM score for prediction of hemorrhagic risk in the pediatric AVM population. METHODS A pediatric database at Boston Children’s Hospital was retrospectively reviewed for all patients with a diagnosis of intracranial AVM. Exclusion criteria included age > 21 years, multiple AVMs, and incomplete clinical/radiographic data. Demographic data and R2eD AVM score calculations were collected for all patients. Univariate binary logistic regression and multivariate stepwise backward elimination models were used to determine factors associated with hemorrhagic presentation. RESULTS A total of 212 AVMs were identified in 212 patients with vascular anomalies from 1995 to 2021, and 144 patients met the inclusion criteria (74 [51.4%] male, 111 [77.1%] White), of whom 87 (60.4%) patients presented with rupture and 122 (84.7%) underwent resection. The mean age at surgery was 12 years (range 3 months to 20 years). The R2eD AVM scoring system was applied to each patient. The score components of size < 3 cm and exclusive deep venous drainage were significantly associated with rupture risk (p < 0.05). The complete model for the R2eD AVM score had an area under the curve of 0.671 (95% CI 0.586–0.757). CONCLUSIONS This study demonstrated poor external validity of the R2eD AVM score in predicting pediatric AVM rupture risk. The results suggest that future studies are warranted to determine a better scoring method to capture pediatric rupture risk, given the significant differences in clinical presentation in pediatric compared with adult AVM patients.

Post-traumatic epidural hematoma (EDH) accounts for 1-3% of pediatric closed head injury admissions. There is a 2.5:1 male predominance. Etiology varies by age; motor vehicle collisions are the primary cause of EDH in adolescents. Post-traumatic EDH accompanies up to 4% of adult head injuries, and is associated with 10% mortality in adults and 5% mortality in children. In North America, standard of care for post-traumatic EDH includes decompressive craniotomy or trepanation via burr hole. Such lifesaving care is typically provided in the operating room by consulting neurosurgery teams or other personnel trained in the use of burr hole equipment.The case of a 17-year-old female patient who presented to a community emergency department (ED) after being involved in a motor vehicle collision is discussed. At the scene of the accident, she refused emergency medical services transport and was brought to the ED via private vehicle. She quickly decompensated in the ED and required intubation. Neurosurgical services were not available and transport to the nearest pediatric trauma center was delayed due to weather. Decompression and drainage of her EDH was accomplished with an EZ-IO® driver and intraosseous needle under virtual guidance of a pediatric neurosurgeon until definitive care could be obtained. The patient made a full neurologic recovery.EDHs have high morbidity and mortality. In settings without access to neurosurgical services, and where ED access to or familiarity with burr hole equipment is limited, the EZ-IO® device may be a temporizing and lifesaving intervention until definitive neurosurgical care can be obtained.

Supplementary Figure 2 from Immunologic Consequences of Signal Transducers and Activators of Transcription 3 Activation in Human Squamous Cell Carcinoma

Paracrine cross-talk between tumor cells and immune cells within the tumor microenvironment underlies local mechanisms of immune evasion. Signal transducer and activator of transcription 3 (STAT3), which is constitutively activated in diverse cancer types, is a key regulator of cytokine and chemokine expression in murine tumors, resulting in suppression of both innate and adaptive antitumor immunity. However, the immunologic effects of STAT3 activation in human cancers have not been studied in detail. To investigate how STAT3 activity in human head and neck squamous cell carcinoma (HNSCC) might alter the tumor microenvironment to enable immune escape, we used small interfering RNA and small-molecule inhibitors to suppress STAT3 activity. STAT3 inhibition in multiple primary and established human squamous carcinoma lines resulted in enhanced expression and secretion of both proinflammatory cytokines and chemokines. Although conditioned medium containing supernatants from human HNSCC inhibited lipopolysaccharide-induced dendritic cell activation in vitro, supernatants from STAT3-silenced tumor cells reversed this immune evasion mechanism. Moreover, supernatants from STAT3-silenced tumor cells were able to stimulate the migratory behavior of lymphocytes from human peripheral blood in vitro. These results show the importance of STAT3 activation in regulating the immunomodulatory mediators by human tumors and further validate STAT3 as a promising target for therapeutic intervention. Cancer Res; 70(16); 6467–76. ©2010 AACR.

Supplementary Figure 4 from Immunologic Consequences of Signal Transducers and Activators of Transcription 3 Activation in Human Squamous Cell Carcinoma

Supplementary Tables 1-2 from Immunologic Consequences of Signal Transducers and Activators of Transcription 3 Activation in Human Squamous Cell Carcinoma

Supplementary Figure 3 from Immunologic Consequences of Signal Transducers and Activators of Transcription 3 Activation in Human Squamous Cell Carcinoma

Supplementary Figure 1 from Immunologic Consequences of Signal Transducers and Activators of Transcription 3 Activation in Human Squamous Cell Carcinoma

Introduction: Moyamoya is a progressive cerebrovascular disease leading to stenosis of arteries located in the circle of Willis which increases risk of hypoperfusion in specific areas of the brain called watershed regions. Using diffusion weighted magnetic resonance imaging (dMRI), adults with moyamoya have significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD) and radial diffusivity (RD) in their white matter compared to controls. These areas of white matter alterations have been associated with cognitive deficits as well. To our knowledge the examination of combined white matter tracts in the watershed regions of the brain in children with moyamoya has not been previously examined. Hypothesis: We hypothesize that children with moyamoya will have higher FA and lower MD and RD in the combined white matter tracts that are in the watershed region compared to control children. Methods: We compared a cohort of 15 children with moyamoya with 24 affected hemispheres without stroke to 25 children controls. We analyzed dMRI data using an unscented Kalman filter (UKF) tractography method and extracted major white matter pathways with a fiber clustering method. We compared the FA, MD, axial diffusivity (AD), and RD of the combined watershed white matter tracts using co-variate adjusted ANOVA. Results: Age and sex were not significantly different between children with moyamoya and controls. For the combined watershed white matter tracts, children with moyamoya had significantly lower FA and higher MD and RD. AD was also higher but not significant compared to control children (Table 1). Conclusion: Lower FA with higher MD and RD is consistent with alterations in white matter tracts concerning for unrecognized white matter injury from hypoperfusion. These dMRI findings could be used as a biomarker for children with moyamoya at risk for cognitive deficits due to hypoperfusion.

Introduction: Perioperative stroke is a major complication of revascularization surgery in patients with moyamoya. Vomiting is common after neurosurgical procedures and may result in acute changes in intracranial pressure and cerebral blood flow. We instituted a standardized perioperative nausea and vomiting protocol for children and young adults with moyamoya undergoing indirect bypass surgery at our institution. Hypothesis: Instituting a standardized perioperative nausea and vomiting protocol will be associated with reduction in the number of perioperative strokes in children with moyamoya undergoing indirect bypass surgery. Methods: We retrospectively reviewed consecutive cases of children and young adults with moyamoya who underwent indirect bypass surgery before and after implementation of a new perioperative nausea and vomiting protocol. We compared the rate of strokes in the perioperative period (post-operative day 0 and 1) in the 41 months following implementation (155 surgically treated hemispheres) to 155 surgically treated hemispheres (over 30 months) prior to implementation using Fisher’s Exact test. Results: The mean age prior to implementation was 8.7 years (SD 5.5 years) and 9.9 years (SD 6.2 years) post implementation which was not significantly different (p=0.17). In the 30 months prior to initiation of the perioperative nausea and vomiting protocol there were 5 strokes in 155 surgically treated hemispheres (3.2%). After initiation of the protocol, there were no strokes in 155 surgically treated hemispheres (p = 0.03). Conclusions: Instituting a standardized perioperative nausea and vomiting protocol was associated with reduction in perioperative strokes in children with moyamoya treated with indirect bypass surgery.

Moyamoya syndrome increases the risk of stroke in sickle cell disease, but revascularization surgery can modify this risk. Collaborative management between hematology and neurosurgery offers effective strategies to reduce stroke risk in these patients. We describe a challenging case where a patient with sickle cell disease undergoing standard of care management as prescribed by the Stroke Prevention Trial in Sickle Cell Anemia and revascularization with pial synangiosis subsequently developed rapidly progressive disease in other cerebral vessels and suffered ischemic hemispheric stroke. This case not only demonstrates the success of management in accordance with the American Heart Association (AHA) and American Stroke Association (ASA) guidelines but also demonstrates critical areas where we lack understanding of disease progression.

Gain of function PIK3CA pathogenic variants have been identified in overgrowth syndromes collectively termed "PIK3CA-related overgrowth spectrum" (PROS). There are no previously reported cases of cerebrovascular venous malformations in PROS syndromes, though somatic activating PIK3CA variants have been identified in extracranial venous malformation. This study was approved by the Institutional Review Boar at Boston Children's Hospital. A 14-year-old female mosaic for the de novo p.R108H pathogenic variant in the PIK3CA gene was found to have a large tumor involving the superior sagittal sinus with mass effect on the motor cortex most consistent with a parafalcine meningioma. She underwent surgical resection with pathology demonstrating a venous malformation. PIK3CA pathogenic variants have been identified in nonsyndromic extracranial venous and lymphatic malformations as well in brain tumors, including glioma and meningioma. However, PIK3CA variants have not previously been identified in purely intracranial venous malformations. This distinction is relevant to treatment decisions, given that mTOR inhibitors may provide an alternative option for noninvasive therapy in cases of suspected venous malformation.

Donor vessel quality can impact the outcome of extracranial-intracranial (EC-IC) bypass. External carotid artery (ECA) disease may produce embolism into the anastomosis and cerebral territory and possibly reduce flow in the superficial temporal artery (STA). Previously reported remedies to ECA stenosis include ECA endarterectomy, stenting, and angioplasty. Clinical presentation A middle-aged patient with chronic left MCA occlusion, progressive ischemic symptoms on maximal medical therapy, and imaging confirmation of compromised hemodynamic reserve was evaluated for EC-IC bypass. Angiography demonstrated severe ECA origin stenosis. An ECA-ICA transposition was performed, primarily to eliminate the risk of emboli and secondarily to possibly improve the STA flow. The patient sustained an excellent radiological and clinical outcome, and the STA donor cut-flow was increased modestly by 22% (45 to 55 mL/min). This case is the first report of an ECA to internal carotid artery transposition as an option in the management of ECA stenosis in preparation for an STA-MCA bypass for the purpose of flow augmentation.

Pediatric hemorrhagic stroke (HS) accounts for a large proportion of childhood strokes, 1 of the top 10 causes of pediatric deaths. Morbidity and mortality lead to significant socio-economic and psychosocial burdens. To understand published data on recognizing and managing children with HS, we conducted a systematic review of the literature presented here. We searched PubMed, Embase, CINAHL and the Cochrane Library databases limited to English language and included 174 studies, most conducted in the USA (52%). Terminology used interchangeably for HS included intraparenchymal/intracranial hemorrhage, spontaneous ICH, and cerebrovascular accident (CVA). Key assessments informing prognosis and management included clinical scoring (Glasgow coma scale), and neuroimaging. HS etiologies reported were systemic coagulopathy (genetic, acquired pathologic, or iatrogenic), or focal cerebrovascular lesions (brain arteriovenous malformations, cavernous malformations, aneurysms, or tumor vascularity). Several scales were used to measure outcome: Glasgow outcome score (GOS), Kings outcome score for head injury (KOSCHI), modified Rankin scale (mRS) and pediatric stroke outcome measure (PSOM). Most studies described treatments of at-risk lesions. Few studies described neurocritical care management including raised ICP, seizures, vasospasm, or blood pressure. Predictors of poor outcome included ethnicity, comorbidity, location of bleed, and hematomagt;2% of total brain volume. Motor and cognitive outcomes followed independent patterns. Few studies reported on cognitive outcomes, rehabilitation, and transition of care models. Interdisciplinary approach to managing HS is urgently needed, informed by larger cohort studies targeting key clinical question (eg development of a field-guide for the clinician managing patients with HS that is reproducible internationally).

Moyamoya is a progressive cerebrovascular disorder that leads to stenosis of the arteries in the distal internal carotid, proximal middle cerebral and proximal anterior cerebral arteries of the circle of Willis. Typically a network of collaterals form to bypass the stenosis and maintain cerebral blood flow. As moyamoya progresses it affects the anterior circulation more commonly than posterior circulation, and cerebral blood flow becomes increasingly reliant on external carotid supply. Children with moyamoya are at increased risk for ischemic symptoms including stroke and transient ischemic attacks (TIA). In addition, cognitive decline may occur over time, even in the absence of clinical stroke. Standard of care for stroke prevention in children with symptomatic moyamoya is revascularization surgery. Treatment of children with asymptomatic moyamoya with revascularization surgery however remains more controversial. Therefore, biomarkers are needed to assist with not only diagnosis but also with determining ischemic risk and identifying best surgical candidates. In this review we will discuss the current knowledge as well as gaps in research in relation to pediatric moyamoya biomarkers including neurologic presentation, cognitive, neuroimaging, genetic and biologic biomarkers of disease severity and ischemic risk.

Background: Cerebrovascular embryologic development is characterized by the presence of four well-described carotid-vertebrobasilar (VB) anastomoses. As the fetal hindbrain matures and the VB system develops, these connections involute, yet some may persist into adulthood. The persistent primitive trigeminal artery (PPTA) is the most common of these anastomoses. In this report, we describe a unique variant of the PPTA and a four-way division of the VB circulation. Case Description: A female in her 70s presented with a Fisher Grade 4 subarachnoid hemorrhage. Catheter angiography revealed a fetal origin of the left posterior cerebral artery (PCA) giving rise to a left P2 aneurysm which was coiled. A PPTA arose from the left internal carotid artery and supplied the distal basilar artery (BA) including the superior cerebellar arteries bilaterally and the right but not left PCA. The mid-BA was atretic and the anterior inferior cerebellar artery-posterior inferior cerebellar artery complexes were fed solely from the right vertebral artery. Conclusion: Our patient’s cerebrovascular anatomy represents a unique variant of the PPTA not well described in the literature. This demonstrates how hemodynamic capture of the distal VB territory by a PPTA is sufficient to prevent fusion of the BA.

BACKGROUND AND PURPOSE Dynamic susceptibility perfusion MR imaging (DSC MRP) has been used to assess changes in cerebral perfusion attributable to vascular stenosis or occlusion that may predict stroke risk. However, DSC MRP is not validated for identifying hemodynamic compromise in the posterior circulation. We investigated the clinical utility of DSC MRP in vertebrobasilar (VB) atherosclerotic disease in the observational VERiTAS study. METHODS VERiTAS enrolled patients with symptomatic ≥50% VB stenosis/occlusion. Posterior circulation hemodynamic status was designated as low or normal based on large vessel flow measured using quantitative magnetic resonance angiography (QMRA) and was predictive of future stroke risk. In this study, DSC MRP conducted concurrently with QMRA was used to evaluate posterior circulation perfusion. The primary outcome was the mean transit time (MTT) and relative cerebral blood volume (rCBV) in the posterior circulation normalized to the anterior circulation, compared between patients with low and normal blood flow as determined on QMRA. RESULTS Twenty-six subjects had 47 DSC MRP studies for review. There was no statistically or clinically significant difference in the rCBV ratio (1.02 vs. .96 P = .89), or MTT ratio (1.04 vs. 1.04 P = .96) relative to normal or low VB territory flow. CONCLUSIONS In this study, we did not find that DSC MRP adequately distinguished between patients with low or normal flow status based on large-vessel flow measurements.

BackgroundBlebs are important secondary structures of intracranial aneurysms associated with increased rupture risk and can affect local wall stress and hemodynamics. Mechanisms of bleb development and evolution are not clearly understood. We investigate the relationship between blebs with different wall characteristics and local hemodynamics and rupture sites.MethodsBlebs with different wall appearances in intra-operative videos were analyzed with image-based computational fluid dynamics. Thin red blebs were compared against thick atherosclerotic/hyperplastic white/yellow blebs. Rupture points were identified in videos of ruptured aneurysms harboring blebs.ResultsThin blebs tended to be closer to the inflow than atherosclerotic blebs of the same aneurysm (P=0.0234). Blebs near the inflow had higher velocity (P=0.0213), vorticity (P=0.0057), shear strain rate (P=0.0084), wall shear stress (WSS) (P=0.0085), and WSS gradient (P=0.0151) than blebs far from the inflow. In a subset of 12 ruptured aneurysms harboring blebs, rupture points were associated with thin blebs in 42% of aneurysms, atherosclerotic blebs in 25%, and were away from blebs in the remaining 33%.ConclusionsNot all blebs are equal; some have thin translucent walls while others have thick atherosclerotic walls. Thin blebs tend to be located closer to the inflow than atherosclerotic blebs. Blebs near the inflow are exposed to stronger flows with higher and spatially variable WSS than blebs far from the inflow which tend to have uniformly lower WSS. Aneurysms can rupture at thin blebs, atherosclerotic blebs, and even away from blebs. Further study of wall failure in aneurysms with different bleb types is needed.

BackgroundEndovascular embolization of cerebral arteriovenous malformations (AVM) with liquid n-butyl cyanoacrylate (n-BCA) serves multiple purposes including AVM occlusion and flow reduction in preparation for other treatment modalities. The objective was to study the clinical, structural, and angiographic factors affecting complications associated with AVM treatment by sequential n-BCA embolizations for nidal occlusion versus quantitative flow reduction in preparation for surgical resection or radiosurgery.MethodsWe performed a retrospective review of all patients who underwent endovascular embolization of cerebral AVM at our institution between 1998 and 2019, during which time the technique of traditional embolization evolved to a strategy of targeted sequential flow reduction guided by serial flow imaging based on quantitative magnetic resonance angiography, in conjunction with a shift away from nidal penetration.ResultsAmong 251 patients, 47.8% of patients presented with ruptured AVM. On average, each patient underwent 2.4 embolizations, for a total of 613 sessions. Major morbidity related to embolization occurred in 18 (7.2%) patients, but this occurred disproportionately in the traditional embolization strategy (n=16, 8%) in contrast with the flow-targeting strategy (n=2, 3.8%). Four patients (1.6%) died in the overall group, and these all occurred with the traditional embolization strategy (2% of 199 patients); no deaths occurred in the flow-targeting strategy (n=52).ConclusionEmbolization with n-BCA targeted to sequential flow reduction and feeder occlusion with limited nidal penetration prior to definitive surgical or radiosurgical treatment can be safely performed with low overall morbidity and mortality.

Object The breadth and complexity of neurovascular pathologies treated with endovascular neurosurgery has expanded dramatically in recent years. Many aneurysms remain difficult to treat safely. Transcirculation (contralateral and/or retrograde) approaches through the circle of Willis are useful alternatives for treating challenging lesions endovascularly. Here, we present a series of patients treated with unconventional transcirculation techniques. Methods A total of six patients were treated: four patients with five aneurysms, one patient with an MCA stroke, and one patient with a meningioma requiring preoperative embolization were initially thought not to be amenable to endovascular treatment. The decision was made to treat these patients with transcirculation approaches. All patients were treated by one interventionist. One aneurysm was located in the cavernous internal carotid artery (ICA), one in the vertebral artery, two in the paraclinoid ICA, and one in a cerebellar AVM feeder vessel were treated. Results Five of six patients (83%) made a full neurologic recovery. Three aneurysms were treated to complete occlusion, one aneurysm was left with small residual neck filling, and one aneurysm was not able to be treated. One patient underwent mechanical thrombectomy of a middle cerebral artery (MCA) embolus and MCA filling was restored after treatment. One patient underwent complete embolization of the deep vascular supply of a meningioma. Conclusions Although many neurovascular pathologies remain unsuitable for endovascular treatment, transcirculation approaches can allow for safe, successful treatment of challenging lesions in select patients.

Background and Purpose Fractal dimension is an objective metric for the notion of structural complexity. We sought to investigate differences in structural complexity between healthy and affected territories of cerebral vasculature in moyamoya, as well as associated scalp vasculature and native transdural collaterals in patients with moyamoya by comparing their respective fractal dimensions. Methods Our cohort consisted of 15 transdural collaterals from 12 patients with unilateral anterior circulation moyamoya. Frames of distal arterial vasculature from internal and external carotid angiograms were selected then automatically segmented and also manually annotated by a cerebrovascular surgeon. In the affected hemisphere, the region with transdural collateral supply was compared to the contralateral region. The resulting skeletonized angiograms were analyzed for their fractal dimensions. Results We found the average fractal dimension (Df) of the moyamoya-side ICA was 1.82 with slightly different means for the anteroposterial (AP) and lateral views (mean = 1.82; mean = 1.81). The overall mean for healthy cerebral vasculature was also found to be 1.82 (AP: mean = 1.83; lateral: mean = 1.81). Mean Df of native transdural collaterals was found to be 1.82 (AP: mean = 1.83; lateral: mean = 1.81). The mean Df difference between autosegmented and manually segmented images was 0.013. Conclusion In accordance with the clinical understanding of moyamoya disease, the distal arterial structural complexity is not affected in moyamoya, and is maintained by transdural collaterals formed by vasculogenesis. Autosegmentation of cerebral vasculature is also shown to be accurate when compared to manual segmentation.

ObjectivesTuberculosis is uncommon in the United States and a rare cause of meningitis in children with severe neurologic consequences. Tuberculous meningitis (TBM) is an even rarer cause of moyamoya syndrome with only a handful of cases previously reported.MethodsWe report the case of a female patient who initially presented at 6 years of age with TBM and developed moyamoya syndrome requiring revascularization surgery.ResultsShe was found to have basilar meningeal enhancement and right basal ganglia infarcts. She was treated with 12 months of antituberculosis therapy and 12 months of enoxaparin and maintained on daily aspirin indefinitely. However, she developed recurrent headaches and transient ischemic attacks and was found to have progressive bilateral moyamoya arteriopathy. At age 11 years, she underwent bilateral pial synangiosis for the treatment of her moyamoya syndrome.DiscussionMoyamoya syndrome is a rare but serious sequalae of TBM and may be more common in pediatric patients. The risk of stroke may be mitigated by pial synangiosis or other revascularization surgeries in carefully selected patients.

Machine learning (ML) has been increasingly used in medicine and neurosurgery. We sought to determine whether ML models can distinguish ruptured from unruptured aneurysms and identify features associated with rupture.We performed a retrospective review of patients with intracranial aneurysms detected on vascular imaging at our institution between 2002 and 2018. The dataset was used to train 3 ML models (random forest, linear support vector machine [SVM], and radial basis function kernel SVM). Relative contributions of individual predictors were derived from the linear SVM model.Complete data were available for 845 aneurysms in 615 patients. Ruptured aneurysms (n = 309, 37%) were larger (mean 6.51 mm vs. 5.73 mm; P = 0.02) and more likely to be in the posterior circulation (20% vs. 11%; P0.001) than unruptured aneurysms. Area under the receiver operating curve was 0.77 for the linear SVM, 0.78 for the radial basis function kernel SVM models, and 0.81 for the random forest model. Aneurysm location and size were the 2 features that contributed most significantly to the model. Posterior communicating artery, anterior communicating artery, and posterior inferior cerebellar artery locations were most highly associated with rupture, whereas paraclinoid and middle cerebral artery locations had the strongest association with unruptured status.ML models are capable of accurately distinguishing ruptured from unruptured aneurysms and identifying features associated with rupture. Consistent with prior studies, location and size show the strongest association with aneurysm rupture.

Background The impact of cerebral aneurysm size on distal intracranial hemodynamics such as arterial pressure and Pulsatility Index is not completely understood, either before or after flow diversion. Objective The aim of the study is to assess the impact of aneurysm size on distal Pulsatility Index and pressure before and after flow diversion. Methods From December 2015, prospective measurement of middle cerebral artery pressure and Pulsatility Index was performed in consecutive patients with unruptured cerebral aneurysms in the cavernous to communicating segments of the internal carotid artery, which were treated with single flow diversion. Pressure and Pulsatility Index were recorded at the M1-segment ipsilateral to the cerebral aneurysm. Ratio of middle cerebral artery to radial arterial pressure (pressure ratio) was calculated to control for variations in systemic blood pressure. Correlations between aneurysm size and pressure ratio and Pulsatility Index were assessed before and after treatment. Results A total of 28 aneurysms were treated. The mean aneurysm size was 7.2 mm. Aneurysm size correlated linearly with systolic pressure ratio (1% pressure ratio increase per mm aneurysm size increase, P = 0.002, r2 = 0.33), mean pressure ratio (0.6% per mm, P = 0.03, r2 = 0.17) and Pulsatility Index (5% Pulsatility Index increase per mm, P = 0.003, r2 = 0.43). After flow diversion, aneurysm size preserved a linear correlation with the systolic pressure ratio (1% per mm, P = 0.004, r2 = 0.28), but not with the mean pressure ratio (0.4% per mm, P = 0.15, r2 2 Conclusion Aneurysm size affects distal hemodynamics: patients with larger aneurysms have increased systolic and mean pressure ratio, and increased Pulsatility Index. After flow diversion, mean pressure ratio and Pulsatility Index no longer associate with the aneurysm size, suggesting an effect of the flow diversion also on distal intracranial hemodynamics.

Donor vessel quality can impact the outcome of extracranial-intracranial (EC-IC) bypass. External carotid artery (ECA) disease may produce embolism into the anastomosis and cerebral territory and possibly reduce flow in the superficial temporal artery (STA). Previously reported remedies to ECA stenosis include ECA endarterectomy, stenting, and angioplasty. Clinical presentation A middle-aged patient with chronic left MCA occlusion, progressive ischemic symptoms on maximal medical therapy, and imaging confirmation of compromised hemodynamic reserve was evaluated for EC-IC bypass. Angiography demonstrated severe ECA origin stenosis. An ECA-ICA transposition was performed, primarily to eliminate the risk of emboli and secondarily to possibly improve the STA flow. The patient sustained an excellent radiological and clinical outcome, and the STA donor cut-flow was increased modestly by 22% (45 to 55 mL/min).This case is the first report of an ECA to internal carotid artery transposition as an option in the management of ECA stenosis in preparation for an STA-MCA bypass for the purpose of flow augmentation.

Atherosclerosis of the internal carotid artery and intracranial vessels can compromise cerebral hemodynamics and cause stroke. Cerebral bypass has a half-century history in augmenting or replacing blood flow the brain. Several trials have investigated various applications of cerebral bypass in flow augmentation for atherosclerotic disease. This review discusses the clinical science of cerebrovascular atherosclerosis to provide the context in which cerebral bypass is currently applied. This includes prior clinical trials, ongoing clinical trials, and consensus guidelines, and is complemented by studies in the physiologic science of cerebrovascular flow. The scientific background is supplemented by the description of the technical art of bypass surgery based on a three-decade experience. Successful application of cerebral bypass to augment flow in atherosclerotic cerebrovascular disease requires correct diagnosis of compromised hemodynamic reserve refractory to medical optimization and an appropriate matching of bypass flow with cerebral demand.

DNA methylation has long been recognized as a tumor-promoting factor when aberrantly regulated in the promoter region of genes. However, the effect of intragenic DNA methylation remains poorly understood on the clinical aspects of cancer. Here, we first evaluated the significance of intragenic DNA methylation for survival outcomes of cancer patients in a genome-wide manner. Glioblastoma patients with hypermethylated intragenic regions exhibited better survival than hypomethylated patients. Enrichment analyses of intragenic DNA methylation profiles with epigenetic signatures prioritized the intragenic DNA methylation of ZMIZ1 as a possible glioblastoma prognostic marker that is independent of MGMT methylation in IDH1 wild-type patients. This intragenic region harbored molecular signatures of alternative transcription across many cell types. Furthermore, we found that the intragenic region of ZMIZ1 can serve as a molecular marker in multiple cancers including astrocytomas, bladder cancer and renal cell carcinoma according to DNA methylation status. Finally, in vitro and in vivo experiments uncovered the role of ZMIZ1 as a driver of tumor cell migration. Altogether, our results identify ZMIZ1 as a prognostic marker in cancer and highlight the clinical significance of intragenic methylation in cancer.

Background Perioperative cerebral infarction is a potential complication of glioma resection, of which insular tumors are at higher risk because of the proximity of middle cerebral artery branches, including the lateral lenticulostriates and long insular arteries. In this study, 3 patients received three-dimensional rotational angiography, which was fused with magnetic resonance imaging (MRI) for frameless stereotactic navigation during dominant-hemisphere insular glioma resection. Methods All patients obtained a preoperative catheter angiogram with a three-dimensional rotational acquisition of the ipsilateral internal carotid artery. The pixel-based axial three-dimensional angiography data, thin-cut structural MRI, tractography from diffusion tensor imaging, and expressive language activation from functional MRI were uploaded into the iPlan software (Brainlab, Heimstetten, Germany) and fused. The target tumor, regional blood vessels, adjacent functional areas, and their associated fiber tracts were segmented and overlaid on the appropriate MRI sequence. This image fusion was used preoperatively to visualize the relationship of the mass with the adjacent vasculature and intraoperatively for frameless stereotactic navigation to optimize preservation of arterial structures. Results Three patients aged 27–60 years with excellent baseline functional status presented with seizures and were found to have a large dominant-hemisphere T2 hyperintense nonenhancing insular mass. Surgical resection was performed using multimodality neuronavigation. None sustained a postoperative arterial infarction or a perioperative neurologic deficit. Conclusions Neuronavigation using a fusion of three-dimensional rotational angiography with MRI is a technique that can be used for preoperative planning and during resection of insular gliomas to optimize preservation of adjacent arteries.

OBJECTIVEParaclinoid aneurysms represent approximately 5% of intracranial aneurysms (Drake et al. [1968]). Visual impairment, which occurs in 16%–40% of patients, is among the most common presentations of these aneurysms (Day [1990], Lai and Morgan [2013], Sahlein et al. [2015], and Silva et al. [2017]). Flow-diverting stents, such as the Pipeline Embolization Device (PED), are increasingly used to treat these aneurysms, in part because of their theoretical reduction of mass effect (Fiorella et al. [2009]). Limited data on paraclinoid aneurysms treated with a PED exist, and few studies have compared outcomes of patients after PED placement with those of patients after clipping or coiling.METHODSThe authors performed a retrospective analysis of 115 patients with an aneurysm of the cavernous to ophthalmic segments of the internal carotid artery treated with clipping, coiling, or PED deployment between January 2011 and March 2017. Postoperative complications were defined as new neurological deficit, aneurysm rupture, recanalization, or other any operative complication that required reintervention.RESULTSA total of 125 paraclinoid aneurysms in 115 patients were treated, including 70 with PED placement, 23 with coiling, and 32 with clipping. Eighteen (14%) aneurysms were ruptured. The mean aneurysm size was 8.2 mm, and the mean follow-up duration was 18.4 months. Most aneurysms were discovered incidentally, but visual impairment, which occurred in 21 (18%) patients, was the most common presenting symptom. Among these patients, 15 (71%) experienced improvement in their visual symptoms after treatment, including 14 (93%) of these 15 patients who were treated with PED deployment. Complete angiographic occlusion was achieved in 89% of the patients. Complications were seen in 17 (15%) patients, including 10 (16%) after PED placement, 2 (9%) after coiling, and 5 (17%) after clipping. Patients with incomplete aneurysm occlusion had a higher rate of procedural complications than those with complete occlusion (p = 0.02). The rate of postoperative visual improvement was significantly higher among patients treated with PED deployment than in those treated with coiling (p = 0.01). The significant predictors of procedural complications were incomplete occlusion (p = 0.03), hypertension, (p = 0.04), and diabetes (p = 0.03).CONCLUSIONSIn a large series in which patient outcomes after treatment of paraclinoid aneurysms were compared, the authors found a high rate of aneurysm occlusion and a comparable rate of procedural complications among patients treated with PED placement compared with the rates among those who underwent clipping or coiling. For patients who presented with visual symptoms, those treated with PED placement had the highest rate of visual improvement. The results of this study suggest that the PED is an effective and safe modality for treating paraclinoid aneurysms, especially for patients who present with visual symptoms.

Disease of the vertebral (VA) and basilar arteries (BA) can lead to stroke of the posterior circulation and may warrant management strategies which differ from the anterior circulation. The mechanism and location of the disease determine its natural history and therefore affect the relative risks and benefits of the possible treatment options. Vertebrobasilar (VB) atherosclerotic disease is a source of both hemodynamic and embolic posterior circulation stroke. Advances in medical therapy have decreased the rate of stroke after initial symptomatic presentation. Antiplatelet therapy, blood pressure control, and optimization of secondary risk factors can reduce recurrent stroke risk in both intracranial and extracranial VB disease. However, symptomatic intracranial disease is still associated with a high risk of subsequent stroke, particularly those with hemodynamic compromise who represent a higher risk population. Patients with hemodynamic impairment may benefit from judicious application of endovascular and microsurgical interventions to augment blood flow. Stenting, angioplasty alone, bypass surgery, and endarterectomy, represent endovascular and surgical tools available to address medically refractory VB disease. Apart from atherosclerotic disease, dissection is another etiology of VB stroke, most frequently affecting the extracranial VA. Treatment is predominantly antithrombotic therapy although surgical or endovascular intervention can be required in rare cases of persistent embolism or hemodynamic compromise. In contrast, extrinsic compromise of the VA represents a separate extracranial pathology and is best treated with mechanistically targeted surgeries or extracranial bypass.