Publications by authors named "Nirav J Patel"

44 Publications

Direct vs Indirect Revascularization in a North American Cohort of Moyamoya Disease.

Neurosurgery 2021 May 6. Epub 2021 May 6.

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Background: In adults with ischemic moyamoya disease (MMD), the efficacy of direct vs indirect revascularization procedures remains a matter of debate.

Objective: To investigate the outcomes of ischemic MMD in a North American cohort treated by direct and indirect revascularizations.

Methods: We retrospectively reviewed medical records of adult patients with MMD with ischemic presentation from 1984 to 2018 at the Brigham and Women's Hospital and Massachusetts General Hospital who underwent either direct or indirect bypasses. Early postoperative events and outcome at more than 6 mo postoperatively were evaluated using multivariable logistic regression analyses. Multivariable Cox proportional hazards regression analyses were used to evaluate delayed ischemic and hemorrhagic events. Analyses were performed per hemisphere.

Results: A total of 95 patients with MMD and 127 hemispheres were included in this study. A total of 3.5% and 8.6% of patients had early surgical complications in the direct and indirect bypass cohorts, respectively (P = .24). Hemispheres with direct bypasses had fewer long-term ischemic and hemorrhagic events at latest follow-up (adjusted hazard ratio [HR] 0.19, 95% confidence interval [CI] 0.058-0.63, P = .007; median follow-up 4.5 [interquartile range, IQR 1-8] yr). There was no difference between the direct and indirect bypass groups when the endpoint was limited to infarction and hemorrhage only (P = .12). There was no difference in outcome (modified Rankin Scale [mRS] ≥ 3) between the 2 cohorts (P = .92).

Conclusion: There was no difference in early postoperative events, long-term infarction or hemorrhage, or clinical outcome between direct and indirect revascularization. However, there was a significant decrease in all ischemic and hemorrhagic events combined in direct revascularizations compared to indirect revascularizations.
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http://dx.doi.org/10.1093/neuros/nyab156DOI Listing
May 2021

Spontaneous hemorrhage after external ventricular drain placement in the setting of low factor VII secondary to liver cirrhosis.

Surg Neurol Int 2020 25;11:403. Epub 2020 Nov 25.

Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, United States.

Background: Alterations in normal coagulation and hemostasis are critical issues that require special attention in the neurosurgical patient. These disorders pose unique challenges in the management of these patients who often have concurrent acute ischemic and hemorrhagic injuries. Although neurosurgical intervention in such cases may be unavoidable and potentially life-saving, these patients should be closely observed after instrumentation.

Case Description: A 57-year-old male with liver cirrhosis secondary to amyloid light-chain amyloidosis was admitted to the intensive care unit for the management of delayed hydrocephalus. An external ventricular drain (EVD) was placed for the treatment and monitoring of hydrocephalus. Five days after EVD placement, a head computed tomography scan revealed a tract hemorrhage. However, on repeated imaging, the size of the hemorrhage continued to increase despite aggressive blood pressure control and several doses of phytonadione. Extensive coagulopathy workup was remarkable for low factor VII levels. In that setting, recombinant activated factor VII was administered to normalize factor VII levels, and the tract hemorrhage stabilized.

Conclusion: To the best of our knowledge, this is the first case of spontaneous hemorrhage after EVD placement in the setting of liver cirrhosis-associated factor VII deficiency. Our case highlights the importance of identifying coagulation disorders in neurosurgical patients at high risk for coagulopathy and closely monitoring them postoperatively.
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http://dx.doi.org/10.25259/SNI_446_2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749959PMC
November 2020

In Reply: The Ruptured Arteriovenous Malformation Grading Scale: An Extension of the Hunt and Hess Scale to Predict Clinical Outcome for Patients With Ruptured Brain Arteriovenous Malformations.

Neurosurgery 2020 Oct 9. Epub 2020 Oct 9.

Department of Neurosurgery Brigham and Women's Hospital School of Medicine Harvard University Boston, Massachusetts.

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http://dx.doi.org/10.1093/neuros/nyaa443DOI Listing
October 2020

Familial Predisposition and Differences in Radiographic Patterns in Spontaneous Nonaneurysmal Subarachnoid Hemorrhage.

Neurosurgery 2021 01;88(2):413-419

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Background: Subarachnoid hemorrhage (SAH) from an intracranial aneurysmal rupture is the most common nontraumatic etiology for SAH, but up to 15% of patients with SAH have no identifiable source.

Objective: To assess familial predisposition to spontaneous nonaneurysmal SAH (naSAH) and to evaluate whether family history affects the severity of presentation and prognosis of this condition.

Methods: We conducted a retrospective analysis of all spontaneous SAH with negative digital subtraction angiography from 2004 to 2018. Patients were divided into 2 groups: patients with first- or second-degree relatives with intracranial aneurysms and patients with no family history. Univariate and multivariate regression analyses were used to study patient presentation, radiographic patterns of hemorrhage, and clinical outcome.

Results: A total of 100 patients met the inclusion criteria. There were no individuals with family history of naSAH. A total of 15 patients (15%) had at least one family member with an intracranial aneurysm, of which 12 (12%) presented as SAH. Patients without family history had a higher percentage of perimesencephalic presentation, whereas those with family history had a higher percentage of nonperimesencephalic SAH presentation (47% vs 13%, odds ratio [OR] 0.17 [95% CI 0.04, 0.81]).

Conclusion: We found a high rate of family history of intracranial aneurysms in patients who presented with naSAH. Although there was no difference in clinical outcome in patients with and without family history, there appears to be a higher percentage of nonperimesencephalic radiographic patterns of SAH in those with family history, suggesting possible different etiologies of these hemorrhages.
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http://dx.doi.org/10.1093/neuros/nyaa396DOI Listing
January 2021

Delayed Relapse of Paracoccidioidomycosis in the Central Nervous System: A Case Report.

Open Forum Infect Dis 2020 Apr 2;7(4):ofaa077. Epub 2020 Mar 2.

Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Paracoccidioidomycosis is a dimorphic fungal infection endemic in Latin America. We report a patient with a history of pulmonary paracoccidioidomycosis who presented with relapsed disease in the central nervous system 4 years after initial treatment. We review current treatment strategies for paracoccidioidomycosis and neuroparacoccidioidomycosis.
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http://dx.doi.org/10.1093/ofid/ofaa077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112725PMC
April 2020

Grapefruit Training Model for Distal Anterior Cerebral Artery Side-to-Side Bypass.

World Neurosurg 2020 06 25;138:39-51. Epub 2020 Feb 25.

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Objective: Simulation models enable trainees to master microsurgical skills before performing surgeries. Vascular bypass is a critical component of cerebrovascular and many nonneurologic procedures. However, most available bypass training models lack important spatial, tactile, and physiologic aspects of real surgery. Animal and placental models provide true physiology but are expensive. While some models adequately simulate superficial temporal artery-middle cerebral artery bypass, there is no model for side-to-side distal anterior cerebral artery bypass. The objective is to create a realistic and inexpensive training model for this important procedure.

Methods: The depth of interhemispheric fissures in cadaver brains was compared with the grapefruit radii. Grapefruits were dissected to simulate the operative field within the deep and narrow interhemispheric fissure. Pericallosal arteries were mimicked with chicken wing vessels or synthetic tubing, with an aquarium pump providing closed circulation. Twelve board-certified neurosurgeons who were given bypass training using the grapefruit model were blindly surveyed on model realism and training suitability.

Results: Grapefruit depths from pith to central column were comparable with interhemispheric cadaveric fissure depths. Approximate preparation time of grapefruit training models was 5-10 minutes. Surveyed neurosurgeons rated the model a better replicate for cerebral artery bypass (P < 0.02) and more challenging than common training models (P < 0.01). They also rated the grapefruit model as likely to be superior for improving surgical skills before surgery (P < 0.05).

Conclusions: This grapefruit model provides a realistic simulation of side-to-side distal anterior cerebral artery bypass procedure that can be inexpensively and easily implemented in nearly any resource environment.
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http://dx.doi.org/10.1016/j.wneu.2020.02.107DOI Listing
June 2020

Correction to: Ancestral Folate Promotes Neuronal Regeneration in Serial Generations of Progeny.

Mol Neurobiol 2020 04;57(4):2072-2073

Department of Neurological Surgery, University of Wisconsin, 600 Highland Avenue, K4/832, Madison, WI, 53792, USA.

The original version of this article unfortunately contained error in Figure 4a to where some of the text was overlapping.
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http://dx.doi.org/10.1007/s12035-020-01886-6DOI Listing
April 2020

Insulin in the Management of Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

World Neurosurg 2020 Apr 16;136:e514-e534. Epub 2020 Jan 16.

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address:

Objective: The role of tight glycemic control in the management of acute ischemic stroke remains uncertain. Our goal is to evaluate the effects of tight glucose control with insulin therapy after acute ischemic stroke.

Methods: We searched PubMed, CENTRAL, and Embase for randomized controlled trials (RCTs) that evaluated the effects of tight glycemic control (70-135 mg/dL) in acute ischemic stroke. Analysis was performed using fixed-effects and random-effects models. Outcomes were death, independence, and modified Rankin Scale (mRS) score at ≥90 days follow-up, and symptomatic or severe hypoglycemia during treatment.

Results: Twelve RCTs including 2734 patients were included. Compared with conventional therapy or placebo, tight glycemic control was associated with similar rates of mortality at ≥90 days follow-up (pooled odds ratio [pOR], 0.99; 95% confidence interval [CI], 0.79-1.22]; I = 0%), independence at ≥90 days follow-up (pOR, 0.95; 95% CI, 0.79-1.14; I = 0%) and mRS scores at ≥90 days follow-up (standardized mean difference, 0.014; 95% CI, -0.15 to 0.17; I = 0%). In contrast, tight glycemic control was associated with increased rates of symptomatic or severe hypoglycemia during treatment (pOR, 5.2; 95% CI, 1.7-15.9; I = 28%).

Conclusions: Tight glucose control after acute ischemic stroke is not associated with improvements in mortality, independence, or mRS score and leads to higher rates of symptomatic or severe hypoglycemia.
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http://dx.doi.org/10.1016/j.wneu.2020.01.056DOI Listing
April 2020

Ancestral Folate Promotes Neuronal Regeneration in Serial Generations of Progeny.

Mol Neurobiol 2020 Apr 10;57(4):2048-2071. Epub 2020 Jan 10.

Department of Neurological Surgery, University of Wisconsin, 600 Highland Avenue, K4/832, Madison, WI, 53792, USA.

Folate supplementation in F0 mating rodents increases regeneration of injured spinal axons in vivo in 4 or more generations of progeny (F1-F4) in the absence of interval folate administration to the progeny. Transmission of the enhanced regeneration phenotype to untreated progeny parallels axonal growth in neuron culture after in vivo folate administration to the F0 ancestors alone, in correlation with differential patterns of genomic DNA methylation and RNA transcription in treated lineages. Enhanced axonal regeneration phenotypes are observed with diverse folate preparations and routes of administration, in outbred and inbred rodent strains, and in two rodent genera comprising rats and mice, and are reversed in F4-F5 progeny by pretreatment with DNA demethylating agents prior to phenotyping. Uniform transmission of the enhanced regeneration phenotype to progeny together with differential patterns of DNA methylation and RNA expression is consistent with a non-Mendelian mechanism. The capacity of an essential nutritional co-factor to induce a beneficial transgenerational phenotype in untreated offspring carries broad implications for the diagnosis, prevention, and treatment of inborn and acquired disorders.
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http://dx.doi.org/10.1007/s12035-019-01812-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125003PMC
April 2020

Anterior Petrosectomy for Resection of Brainstem Cavernous Malformation.

World Neurosurg 2020 03 29;135. Epub 2019 Nov 29.

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Brainstem cavernous malformations are uncommon vascular lesions that require complex surgical approaches. The case described in this video involved a 23-year-old male who presented with repeated, symptomatic episodes of bleeding of pontomedullary cavernous malformation, which was resected. The anterior petrosectomy approach is detailed in Video 1, highlighting middle fossa triangles and their boundaries, as well as important safety techniques. Postoperative imaging depicted complete resection of the cavernoma. Six months after surgery, the patient reported complete resolution of his symptoms.
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http://dx.doi.org/10.1016/j.wneu.2019.11.138DOI Listing
March 2020

Intracranial Hemorrhage from Meningioma: 2 Novel Risk Factors.

World Neurosurg 2020 Mar 4;135:217-221. Epub 2019 Nov 4.

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address:

Background: Meningiomas are the most common benign intracranial tumor. Although meningiomas are slow growing and potentially highly vascularized, hemorrhage of these tumors is rare. We propose 2 novel modifiable risk factors that may provoke intratumoral hemorrhage of a World Health Organization grade I meningioma.

Case Description: We outline the clinical presentation of a 56-year-old female with spontaneous subarachnoid hemorrhage with intraventricular extension in a coma from a petroclival meningioma taking escitalopram for depression and high-dose estrogen replacement therapy for menopause. Pathology confirmed the diagnosis of World Health Organization grade I meningioma. Postoperatively, the patient declined neurologically and developed vasospasm of the basilar artery, as well as seizures, fever, and new-onset atrial fibrillation.

Conclusions: Spontaneous hemorrhage of meningiomas is a rare event. Known risk factors are age older than 70 or younger than 30; intraventricular or convexity location; malignant, fibrous, or angioblastic histopathology; and presence of hypertension, anticoagulation therapy, and traumatic brain injury. We propose 2 new risk factors to be considered that may predispose to hemorrhage of a meningioma: serotonin-modulating therapy and high-dose estrogen-replacement.
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http://dx.doi.org/10.1016/j.wneu.2019.10.173DOI Listing
March 2020

Predictive Score of Adverse Events After Carotid Endarterectomy: The NSQIP Registry Carotid Endarterectomy Scale.

J Am Heart Assoc 2019 11 30;8(21):e013412. Epub 2019 Oct 30.

Department of Neurosurgery Brigham and Women's Hospital Harvard Medical School Boston MA.

Background The goal of this study was to create a comprehensive, integer-weighted predictive scale of adverse events after carotid endarterectomy (CEA), which may augment risk stratification and patient counseling. Methods and Results The targeted carotid files from the prospective NSQIP (National Surgical Quality Improvement Program) registry (2011-2013) comprised the derivation population. Multivariable logistic regression evaluated predictors of a 30-day adverse event (stroke, myocardial infarction, or death), the effect estimates of which were used to build a weighted predictive scale that was validated using the 2014 to 2015 NSQIP registry release. A total of 10 766 and 8002 patients were included in the derivation and the validation populations, in whom 4.0% and 3.7% developed an adverse event, respectively. The NSQIP registry CEA scale included 14 variables; the highest points were allocated for insulin-dependent diabetes mellitus, high-risk cardiac physiological characteristics, admission source other than home, an emergent operation, American Society of Anesthesiologists' classification IV to V, modified Rankin Scale score ≥2, and presentation with a stroke. NSQIP registry CEA score was predictive of an adverse event (concordance=0.67), stroke or death (concordance=0.69), mortality (concordance=0.76), an extended hospitalization (concordance=0.73), and a nonroutine discharge (concordance=0.83) in the validation population, as well as among symptomatic and asymptomatic subgroups (<0.001). In the validation population, patients with an NSQIP registry CEA scale score >8 and 17 had 30-day stroke or death rates >3% and 6%, the recommended thresholds for asymptomatic and symptomatic patients, respectively. Conclusions The NSQIP registry CEA scale predicts adverse outcomes after CEA and can risk stratify patients with both symptomatic and asymptomatic carotid stenosis using different thresholds for each population.
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http://dx.doi.org/10.1161/JAHA.119.013412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6898838PMC
November 2019

The Ruptured Arteriovenous Malformation Grading Scale (RAGS): An Extension of the Hunt and Hess Scale to Predict Clinical Outcome for Patients With Ruptured Brain Arteriovenous Malformations.

Neurosurgery 2020 08;87(2):193-199

Department of Neurosurgery, Brigham and Women's Hospital, School of Medicine, Harvard University, Boston, Massachusetts.

Background: Arteriovenous malformation (AVM) rupture is highly morbid. Outcomes after AVM rupture differ from other types of brain hemorrhage. There are no specific widely used grading systems designed to predict clinical outcome after AVM rupture.

Objective: To develop an all-comers scoring system to grade patients with AVM rupture and predict clinical outcome more accurately than grading systems currently in use.

Methods: We retrospectively reviewed patients who presented to our institution with a ruptured AVM. Using change in modified Rankin Score (mRS) as our response variable, we generated an ordinal logistic regression model to test for significant predictor variables. The full model was sequentially condensed until the simplest model with the highest area under the receiver operating curve (AUROC) was achieved.

Results: A total of 115 patients who presented with ruptured AVMs were included in the study, with a mean follow-up time of 4 yr. The Ruptured AVM Grading Scale (RAGS) consists of the Hunt and Hess (HH) score (1-5), patient age (<35 = 0, 35-70 = 1, and >70 = 2), deep venous drainage (1), and eloquence (1). The RAGS score outperformed other neurosurgical grading scales in predicting change in mRS, with an AUROC greater than 0.80 across all follow-up periods.

Conclusion: The RAGS score is a simple extension of the HH scale that predicts clinical outcome after AVM rupture more accurately than other grading systems.
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http://dx.doi.org/10.1093/neuros/nyz404DOI Listing
August 2020

Periprocedural intracranial hemorrhage after embolization of cerebral arteriovenous malformations: a meta-analysis.

J Neurosurg 2019 Sep 13:1-11. Epub 2019 Sep 13.

1Department of Neurological Surgery, Brigham and Women's Hospital.

Objective: The primary goal of the treatment of cerebral arteriovenous malformations (AVMs) is angiographic occlusion to eliminate future hemorrhage risk. Although multimodal treatment is increasingly used for AVMs, periprocedural hemorrhage after transarterial embolization is a potential endovascular complication that is only partially understood and merits quantification.

Methods: Searching the period between 1990 and 2019, the authors of this meta-analysis queried the PubMed and Embase databases for studies reporting periprocedural hemorrhage (within 30 days) after liquid embolization (using cyanoacrylate or ethylene vinyl alcohol copolymer) of AVMs. Random effects meta-analysis was used to evaluate the pooled rate of flow-related hemorrhage (those attributed to alterations in AVM dynamics), technical hemorrhage (those related to procedural complications), and total hemorrhage. Meta-regression was used to analyze the study-level predictors of hemorrhage, including patient age, Spetzler-Martin grade, hemorrhagic presentation, embolysate used, intent of treatment (adjuvant vs curative), associated aneurysms, endovascular angiographic obliteration, year of study publication, and years the procedures were performed.

Results: A total of 98 studies with 8009 patients were included in this analysis, and the mean number of embolization sessions per patient was 1.9. The pooled flow-related and total periprocedural hemorrhage rates were 2.0% (95% CI 1.5%-2.4%) and 2.6% (95% CI 2.1%-3.0%) per procedure and 3.4% (95% CI 2.6%-4.2%) and 4.8% (95% CI 4.0%-5.6%) per patient, respectively. The mortality and morbidity rates associated with hemorrhage were 14.6% and 45.1%, respectively. Subgroup analyses revealed a pooled total hemorrhage rate per procedure of 1.8% (95% CI 1.0%-2.5%) for adjuvant (surgery or radiosurgery) and 4.6% (95% CI 2.8%-6.4%) for curative intent. The treatment of aneurysms (p = 0.04) and larger patient populations (p < 0.001) were significant predictors of a lower hemorrhage rate, whereas curative intent (p = 0.04), angiographic obliteration achieved endovascularly (p = 0.003), and a greater number of embolization sessions (p = 0.03) were significant predictors of a higher hemorrhage rate. There were no significant differences in periprocedural hemorrhage rates according to the years evaluated or the embolysate utilized.

Conclusions: In this study-level meta-analysis, periprocedural hemorrhage was seen after 2.6% of transarterial embolization procedures for cerebral AVMs. The adjuvant use of endovascular embolization, including in the treatment of associated aneurysms and in the presurgical or preradiosurgical setting, was a study-level predictor of significantly lower hemorrhage rates, whereas more aggressive embolization involving curative intent and endovascular angiographic obliteration was a predictor of a significantly higher total hemorrhage rate.
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http://dx.doi.org/10.3171/2019.5.JNS183204DOI Listing
September 2019

Machine Learning Models can Detect Aneurysm Rupture and Identify Clinical Features Associated with Rupture.

World Neurosurg 2019 Nov 9;131:e46-e51. Epub 2019 Jul 9.

Departments of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts, USA; Computational Neuroscience Outcomes Center, Brigham and Women's Hospital, Boston, Massachusetts, USA. Electronic address:

Background: 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.

Methods: 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.

Results: 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%; P < 0.001) 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.

Conclusions: 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.
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http://dx.doi.org/10.1016/j.wneu.2019.06.231DOI Listing
November 2019

Tentorial Venous Anatomy: Cadaveric and Radiographic Study with Discussion of Origin and Surgical Significance.

World Neurosurg 2019 Nov 9;131:e38-e45. Epub 2019 Jul 9.

Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Background: Described variations of tentorial venous anatomy impact surgical sectioning of the tentorium in skull base approaches; however, described configurations do not consistently explain postoperative complications. To understand the outcomes of 2 clinical cases we studied the tentorial venous anatomy of 2 cadavers.

Methods: The venous anatomy of the tentorium isolated in 2 uninjected fresh cadaver head specimens with preserved bridging veins was observed by transillumination before and after methylene blue injection of the dural sinuses and tentorial veins. Our findings in cadavers were applied to explain the clinical and radiologic (magnetic resonance imaging and computed tomographic venography) findings in the 2 cases presented.

Results: A consistent transtentorial venous system, arising from transverse and straight sinuses, communicating with supra- and infratentorial bridging veins was seen in the cadaver and patient radiography (magnetic resonance imaging and computed tomographic venography). Our first patient had a cerebellar venous infarct from compromise of the venous drainage from the adjacent brain after ligation of a temporal lobe bridging vein to the tentorium. Our second patient suffered no clinical effects from bilateral transverse sinus occlusion due to drainage through the accessory venous system within the tentorium.

Conclusions: Herein, we elaborate on transtentorial venous anatomy. These veins, previously reported to obliterate in completed development of the tentorium, remain patent with consistent observed configuration. The same transtentorial venous system was observed in both cases and provided insight to their outcomes. These findings emphasize the importance of the transtentorial venous system physiologically and in surgical approaches.
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http://dx.doi.org/10.1016/j.wneu.2019.06.232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819248PMC
November 2019

Adverse events after clipping of unruptured intracranial aneurysms: the NSQIP unruptured aneurysm scale.

J Neurosurg 2019 Mar 15;132(4):1123-1132. Epub 2019 Mar 15.

Objective: The complex decision analysis of unruptured intracranial aneurysms entails weighing the benefits of aneurysm repair against operative risk. The goal of the present analysis was to build and validate a predictive scale that identifies patients with the greatest odds of a postsurgical adverse event.

Methods: Data on patients who underwent surgical clipping of an unruptured aneurysm were extracted from the prospective National Surgical Quality Improvement Program registry (NSQIP; 2007-2014); NSQIP does not systematically collect data on patients undergoing intracranial endovascular intervention. Multivariable logistic regression evaluated predictors of any 30-day adverse event; variables screened included patient demographics, comorbidities, functional status, preoperative laboratory values, aneurysm location/complexity, and operative time. A predictive scale was constructed based on statistically significant independent predictors, which was validated using both NSQIP (2015-2016) and the Nationwide Inpatient Sample (NIS; 2002-2011).

Results: The NSQIP unruptured aneurysm scale was proposed: 1 point was assigned for a bleeding disorder; 2 points for age 51-60 years, cardiac disease, diabetes mellitus, morbid obesity, anemia (hematocrit < 36%), operative time 240-330 minutes; 3 points for leukocytosis (white blood cell count > 12,000/μL) and operative time > 330 minutes; and 4 points for age > 60 years. An increased score was predictive of postoperative stroke or coma (NSQIP: p = 0.002, C-statistic = 0.70; NIS: p < 0.001, C-statistic = 0.61), a medical complication (NSQIP: p = 0.01, C-statistic = 0.71; NIS: p < 0.001, C-statistic = 0.64), and a nonroutine discharge (NSQIP: p < 0.001, C-statistic = 0.75; NIS: p < 0.001, C-statistic = 0.66) in both validation populations. Greater score was also predictive of increased odds of any adverse event, a major complication, and an extended hospitalization in both validation populations (p ≤ 0.03).

Conclusions: The NSQIP unruptured aneurysm scale may augment the risk stratification of patients undergoing microsurgical clipping of unruptured cerebral aneurysms.
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http://dx.doi.org/10.3171/2018.12.JNS182873DOI Listing
March 2019

Monogenic, Polygenic, and MicroRNA Markers for Ischemic Stroke.

Mol Neurobiol 2019 Feb 8;56(2):1330-1343. Epub 2018 Jun 8.

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.

Ischemic stroke (IS) is a leading disease with high mortality and disability, as well as with limited therapeutic window. Biomarkers for earlier diagnosis of IS have long been pursued. Family and twin studies confirm that genetic variations play an important role in IS pathogenesis. Besides DNA mutations found previously by genetic linkage analysis for monogenic IS (Mendelian inheritance), recent studies using genome-wide associated study (GWAS) and microRNA expression profiling have resulted in a large number of DNA and microRNA biomarkers in polygenic IS (sporadic IS), especially in different IS subtypes and imaging phenotypes. The present review summarizes genetic markers discovered by clinical studies and discusses their pathogenic molecular mechanisms involved in developmental or regenerative anomalies of blood vessel walls, neuronal apoptosis, excitotoxic death, inflammation, neurogenesis, and angiogenesis. The possible impact of environment on genetics is addressed as well. We also include a perspective on further studies and clinical application of these IS biomarkers.
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http://dx.doi.org/10.1007/s12035-018-1055-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358039PMC
February 2019

Comparison of flow diversion with clipping and coiling for the treatment of paraclinoid aneurysms in 115 patients.

J Neurosurg 2018 Jun 1:1-8. Epub 2018 Jun 1.

1Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts; and.

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.
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http://dx.doi.org/10.3171/2018.1.JNS171774DOI Listing
June 2018

Thrombectomy for late occlusion of high flow extracranial-intracranial saphenous vein bypass graft after 27 years of patency.

J Neurointerv Surg 2018 Nov 7;10(11):e27. Epub 2018 Apr 7.

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

High flow extracranial-intracranial (EC-IC) bypass with a saphenous vein graft (SVG) has been used for more than 40 years in patients with giant aneurysms of the posterior circulation refractory to medical management, and has demonstrated high long term patency rates. We report the case of a patient treated with external carotid artery (ECA)-posterior cerebral artery SVG bypass in 1989 who presented 27 years later with paresthesias and confusion, and was found to have partial occlusion of her SVG bypass graft and a basilar occlusion. She was treated with mechanical thrombectomy of the basilar occlusion via the partially thrombosed graft, the first report of such a procedure through a high flow posterior circulation EC-IC SVG, resulting in improvement of the patient's neurologic examination. At 27 years, this is the longest reported delay in thrombosis of a high flow SVG bypass graft, highlighting the long term patency of these grafts and the feasibility of thrombectomy through occluded bypass grafts.
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http://dx.doi.org/10.1136/neurintsurg-2017-013670.repDOI Listing
November 2018

Results of Surgery for Low-Grade Brain Arteriovenous Malformation Resection by Early Career Neurosurgeons: An Observational Study.

Neurosurgery 2019 03;84(3):655-661

Department of Clinical Medicine, Macquarie University, New South Wales, Australia.

Background: For sustainability of arteriovenous malformation (AVM) surgery, results from early career cerebrovascular neurosurgeons (ECCNs) must be acceptably safe.

Objective: To determine whether ECCNs performance of Spetzler-Ponce Class A AVM (SPC A) resection can be acceptably safe.

Methods: ECCNs completing a cerebrovascular fellowship (2004-2015) with the last author were included. Inclusion of the ECCN cases occurred if they: had a prospective database of all AVM cases since commencing independent practice; were the primary surgeon on SPC A; and had made the significant management decisions. All SPC A surgical cases from the beginning of the ECCN's independent surgical practice to a maximum of 8 yr were included. An adverse outcome was considered a complication of surgery leading to a new permanent neurological deficit with a last modified Rankin Scale score >1. A cumulative summation (Cusum) plot examined the performance of each surgery. The highest acceptable level of adverse outcomes for the Cusum was 3.3%, derived from the upper 95% confidence interval of the last author's reported series.

Results: Six ECCNs contributed 110 cases for analysis. The median number of SPC A cases operated by each ECCN was 16.5 (range 4-40). Preoperative embolization was performed in 5 (4.5%). The incidence of adverse outcomes was 1.8% (95% confidence interval: <0.01%-6.8%). At no point during the accumulated series did the combined cohort become unacceptable by the Cusum plot.

Conclusion: ECCNs with appropriate training appointed to large-volume cerebrovascular centers can achieve results for surgery for SPC A that are not appreciably worse than those published from high-volume neurosurgeons.
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http://dx.doi.org/10.1093/neuros/nyy088DOI Listing
March 2019

Resection of a Retrochiasmatic Craniopharyngioma by Combined Modified Orbital Craniotomy and Transnasal Endoscopic Techniques.

J Neurol Surg B Skull Base 2018 Apr 28;79(Suppl 3):S243-S244. Epub 2018 Feb 28.

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States.

A 20-year-old patient presented with hydrocephalus but intact vision and hormone function. The MRI showed a large seller, suprasellar and third ventricular mass. We chose a combined approach utilizing the translyvian, lamina terminals route, with a possible interhemispheric approach. But, we also utilized a transnasal endoscopic approach for the tumor that remained below the diaphragma sellae. The patient did well, with complete tumor resection via a staged approach, but did require hormone replacement. The link to the video can be found at: https://youtu.be/yzpfOxzI4cQ .
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http://dx.doi.org/10.1055/s-0038-1623519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5868925PMC
April 2018

Thrombectomy for late occlusion of high flow extracranial-intracranial saphenous vein bypass graft after 27 years of patency.

BMJ Case Rep 2018 Mar 8;2018. Epub 2018 Mar 8.

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

High flow extracranial-intracranial (EC-IC) bypass with a saphenous vein graft (SVG) has been used for more than 40 years in patients with giant aneurysms of the posterior circulation refractory to medical management, and has demonstrated high long term patency rates. We report the case of a patient treated with external carotid artery (ECA)-posterior cerebral artery SVG bypass in 1989 who presented 27 years later with paresthesias and confusion, and was found to have partial occlusion of her SVG bypass graft and a basilar occlusion. She was treated with mechanical thrombectomy of the basilar occlusion via the partially thrombosed graft, the first report of such a procedure through a high flow posterior circulation EC-IC SVG, resulting in improvement of the patient's neurologic examination. At 27 years, this is the longest reported delay in thrombosis of a high flow SVG bypass graft, highlighting the long term patency of these grafts and the feasibility of thrombectomy through occluded bypass grafts.
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http://dx.doi.org/10.1136/bcr-2017-013670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5847895PMC
March 2018

Endovascular Renal Artery Stent Retriever Embolectomy in a Young Patient With Cardiac Myxoma: Case Report and Review of the Literature.

Vasc Endovascular Surg 2018 Jan 21;52(1):70-74. Epub 2017 Nov 21.

1 Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Purpose: Cardiac myxomas are common tumors of the heart with disproportionate impact on young patients, occasionally with dramatic systemic dissemination of tumor emboli with catastrophic multiorgan system ischemia. The coincident comorbidities can increase the risk of traditional treatments for tumor embolus in each region.

Case Report: A young patient with previously unknown cardiac myxoma presented with seizure and was found to have stress cardiomyopathy, multiple cerebral large vessel occlusions with acute ischemic stroke, bilateral lower extremity tumor emboli and rhabdomyolysis, and renal tumor embolus with acute tubular necrosis. We describe a multidisciplinary approach applying cerebrovascular stent retriever devices in tumor embolectomy of the renal artery of a young patient with systemic morbidity, preventing safe laparotomy for open surgical tumor embolectomy.

Conclusion: We describe 2-month renal function outcomes and the considerations in applying a neuroendovascular mechanical thrombectomy device within the renal artery. This was a radiographically successful technique and her renal function appears to be improving at the 2-month follow-up, although this is complicated by other renal insults and support.
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http://dx.doi.org/10.1177/1538574417739746DOI Listing
January 2018

Direct Visualization of Arterial Emboli in Moyamoya Syndrome.

Front Neurol 2017 24;8:425. Epub 2017 Aug 24.

Brigham and Women's Hospital, Department of Neurosurgery, Harvard Medical School, Boston, MA, United States.

Background: Hemodynamic insufficiency is often considered the cause of ischemic stroke in patients with moyamoya syndrome. While high-intensity transient signals (HITS) on transcranial Doppler (TCD) have been reported in this population, the relationship between these signals and ischemic symptoms is not clearly established. Accordingly, current treatment is directed at improving perfusion.

Clinical Presentation: We present two patients with symptoms of cerebral ischemia and angiographic findings of moyamoya syndrome. In each case, ischemia may have been caused by either hypoperfusion or embolization. Patient A presented with multifocal right middle cerebral artery (MCA) territory infarctions and angiographic findings consistent with moyamoya disease. She underwent right superficial temporal artery-MCA bypass. Intra-operatively, embolic material was observed and recorded traveling through the recipient MCA branch artery on two occasions. Postoperative TCD demonstrated HITS that resolved with uptitration of antiplatelet therapy. Patient B presented with multifocal, embolic-appearing left MCA infarctions, and unilateral angiographic moyamoya syndrome. She was found to have HITS in the left MCA, which eventually resolved with a combination of antiplatelets and anticoagulation.

Conclusion: Hemodynamic compromise may not be the only cause of brain infarction in patients with moyamoya syndrome. Observations from these two patients provide both direct visualization and TCD evidence of embolization as a potential etiology for brain ischemia. Future investigations into the role of antithrombotic agents should be considered.
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http://dx.doi.org/10.3389/fneur.2017.00425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609634PMC
August 2017

Protection of melatonin in experimental models of newborn hypoxic-ischemic brain injury through MT1 receptor.

J Pineal Res 2018 Jan 23;64(1). Epub 2017 Oct 23.

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

The function of melatonin as a protective agent against newborn hypoxic-ischemic (H-I) brain injury is not yet well studied, and the mechanisms by which melatonin causes neuroprotection in neurological diseases are still evolving. This study was designed to investigate whether expression of MT1 receptors is reduced in newborn H-I brain injury and whether the protective action of melatonin is by alterations of the MT1 receptors. We demonstrated that there was significant reduction in MT1 receptors in ischemic brain of mouse pups in vivo following H-I brain injury and that melatonin offers neuroprotection through upregulation of MT1 receptors. The role of MT1 receptors was further supported by observation of increased mortality in MT1 knockout mice following H-I brain injury and the reversal of the inhibitory role of melatonin on mitochondrial cell death pathways by the melatonin receptor antagonist, luzindole. These data demonstrate that melatonin mediates its neuroprotective effect in mouse models of newborn H-I brain injury, at least in part, by the restoration of MT1 receptors, the inhibition of mitochondrial cell death pathways and the suppression of astrocytic and microglial activation.
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http://dx.doi.org/10.1111/jpi.12443DOI Listing
January 2018

Vision outcomes in patients with paraclinoid aneurysms treated with clipping, coiling, or flow diversion: a systematic review and meta-analysis.

Neurosurg Focus 2017 Jun;42(6):E15

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

OBJECTIVE Patients with paraclinoid aneurysms commonly present with visual impairment. They have traditionally been treated with clipping or coiling, but flow diversion (FD) has recently been introduced as an alternative treatment modality. Although there is still initial aneurysm thrombosis, FD is hypothesized to reduce mass effect, which may decompress the optic nerve when treating patients with visually symptomatic paraclinoid aneurysms. The authors performed a meta-analysis to compare vision outcomes following clipping, coiling, or FD of paraclinoid aneurysms in patients who presented with visual impairment. METHODS A systematic literature review was performed using the PubMed and Web of Science databases. Studies published in English between 1980 and 2016 were included if they reported preoperative and postoperative visual function in at least 5 patients with visually symptomatic paraclinoid aneurysms (cavernous segment through ophthalmic segment) treated with clipping, coiling, or FD. Neuroophthalmological assessment was used when reported, but subjective patient reports or objective visual examination findings were also acceptable. RESULTS Thirty-nine studies that included a total of 2458 patients (520 of whom presented with visual symptoms) met the inclusion criteria, including 307 visually symptomatic cases treated with clipping (mean follow-up 26 months), 149 treated with coiling (mean follow-up 17 months), and 64 treated with FD (mean follow-up 11 months). Postoperative vision in these patients was classified as improved, unchanged, or worsened compared with preoperative vision. A pooled analysis showed preoperative visual symptoms in 38% (95% CI 28%-50%) of patients with paraclinoid aneurysms. The authors found that vision improved in 58% (95% CI 48%-68%) of patients after clipping, 49% (95% CI 38%-59%) after coiling, and 71% (95% CI 55%-84%) after FD. Vision worsened in 11% (95% CI 7%-17%) of patients after clipping, 9% (95% CI 2%-18%) after coiling, and 5% (95% CI 0%-20%) after FD. New visual deficits were found in patients with intact baseline vision at a rate of 1% (95% CI 0%-3%) for clipping, 0% (95% CI 0%-2%) for coiling, and 0% (95% CI 0%-2%) for FD. CONCLUSIONS To the authors' knowledge, this is the first meta-analysis to assess vision outcomes after treatment for paraclinoid aneurysms. The authors found that 38% of patients with these aneurysms presented with visual impairment. These data also demonstrated a high rate of visual improvement after FD without a significant difference in the rate of worsened vision or iatrogenic visual impairment compared with clipping and coiling. These findings suggest that FD is an effective option for treatment of visually symptomatic paraclinoid aneurysms.
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http://dx.doi.org/10.3171/2017.3.FOCUS1718DOI Listing
June 2017

Surgical Treatment of a Double Origin Posterior Inferior Cerebellar Artery Aneurysm and Insights From Embryology: Case Report and Literature Review.

Oper Neurosurg (Hagerstown) 2017 06;13(3):E8-E12

Background And Importance: Aneurysms affecting double origin (DO) posterior inferior cerebellar artery (PICA) variants are rare. Most reports describe endovascular occlusion of the affected branch to treat the aneurysm, but we describe a patient in which open surgical sacrifice of 1 branch resulted in insufficient perfusion.

Clinical Presentation: We report the only case of open surgical treatment of an aneurysm affecting a leg of a DOPICA. A 42-year-old woman presenting with the worst headache of her life was found to have a DOPICA aneurysm and initially treated by trapping the aneurysm. Intraoperative indocyanine green imaging revealed insufficient perfusion through the caudal branch, which was remediated by end-to-end anastomosis to preserve flow through both origins. The patient made a full recovery.

Conclusion: Treating a DOPICA aneurysm by sacrificing 1 of the origins is not possible for all patients. This first report of open surgical treatment of a DOPICA leg aneurysm suggests that 1 or both branches may be required for sufficient perfusion, and the unique embryology of DOPICA development suggests a possible mechanism.
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http://dx.doi.org/10.1093/ons/opx002DOI Listing
June 2017

Phosphatidylserine Translocation after Radiosurgery in an Animal Model of Arteriovenous Malformation.

Radiat Res 2017 06 17;187(6):701-707. Epub 2017 Apr 17.

a   Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, New South Wales, Australia.

Phosphatidylserine (PS) is asymmetrically distributed across the plasma membrane, located predominantly on the inner leaflet in healthy cells. Translocation of PS to the outer leaflet makes it available as a target for biological therapies. We examined PS translocation after radiosurgery in an animal model of brain arteriovenous malformation (AVM). An arteriovenous fistula was created by end-to-side anastomosis of the left external jugular vein to the common carotid artery in 6-week-old, male Sprague Dawley rats. Six weeks after AVM creation, 15 rats underwent Gamma Knife stereotactic radiosurgery receiving a single 15 Gy dose to the margin of the fistula; 15 rats received sham treatment. Externalization of PS was examined by intravenous injection of a PS-specific near-infrared probe, PSVue-794, and in vivo fluorescence optical imaging at 1, 7, 21, 42, 63 and 84 days postirradiation. Fluorescent signaling indicative of PS translocation to the luminal cell surface accumulated in the AVM region, in both irradiated and nonirradiated animals, at all time points. Fluorescence was localized specifically to the AVM region and was not present in any other anatomical sites. Translocated PS increased over time in irradiated rats (P < 0.001) but not in sham-irradiated rats and this difference reached statistical significance at day 84 (P < 0.05). In summary, vessels within the mature rat AVM demonstrate elevated PS externalization compared to normal vessels. A single dose of ionizing radiation can increase PS externalization in a time-dependent manner. Strict localization of PS externalization within the AVM region suggests that stereotactic radiosurgery can serve as an effective priming agent and PS may be a suitable candidate for vascular-targeting approaches to AVM treatment.
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http://dx.doi.org/10.1667/RR14646.1DOI Listing
June 2017