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Effect of Prior Embolization on Outcomes After Stereotactic Radiosurgery for Pediatric Brain Arteriovenous Malformations: An International Multicenter Study

Burke, Rebecca M; Chen, Ching-Jen; Ding, Dale; Buell, Thomas J; Sokolowski, Jennifer; Sheehan, Kimball A; Lee, Cheng-Chia; Sheehan, Darrah E; Kano, Hideyuki; Kearns, Kathryn N; Tzeng, Shih-Wei; Yang, Huai-Che; Huang, Paul P; Kondziolka, Douglas; Ironside, Natasha; Mathieu, David; Iorio-Morin, Christian; Grills, Inga S; Feliciano, Caleb; Barnett, Gene; Starke, Robert M; Lunsford, L Dade; Sheehan, Jason P
BACKGROUND:Pediatric brain arteriovenous malformations (AVMs) are a significant cause of morbidity but the role of multimodal therapy in the treatment of these lesions is not well understood. OBJECTIVE:To compare the outcomes of stereotactic radiosurgery (SRS) with and without prior embolization for pediatric AVMs. METHODS:We retrospectively evaluated the International Radiosurgery Research Foundation pediatric AVM database. AVMs were categorized, based on use of pre-embolization (E + SRS) or lack thereof (SRS-only). Outcomes were compared in unadjusted and inverse probability weight (IPW)-adjusted models. Favorable outcome was defined as obliteration without post-SRS hemorrhage or permanent radiation-induced changes (RIC). RESULTS:The E + SRS and SRS-only cohorts comprised 91 and 448 patients, respectively. In unadjusted models, the SRS-only cohort had higher rates of obliteration (68.5% vs 43.3%,  < .001) and favorable outcome (61.2% vs 36.3%, P < .001) but a lower rate of symptomatic RIC (9.0% vs 16.7%, P = .031). The IPW-adjusted rates of every outcome were similar between the 2 cohorts. However, cumulative obliteration rates at 3, 5, 8, and 10 yr remained higher in the absence of prior embolization (46.3%, 64.6%, 72.6%, and 77.4% for SRS-only vs 24.4%, 37.2%, 44.1%, and 48.7% for E + SRS cohorts, respectively; SHR = 0.449 [0.238-0.846], P = .013). CONCLUSION:Embolization appears to decrease cumulative obliteration rates after SRS for pediatric AVMs without affecting the risk of post-treatment hemorrhage or adverse radiation effects arguing against the routine use of pre-SRS embolization. While endovascular therapy can be considered for occlusion of high-risk angioarchitectural features prior to SRS, future studies are necessary to clarify its role.
PMID: 34333653
ISSN: 1524-4040
CID: 5026552

Remodeling of the Posterior Cerebral Artery P1-Segment after Pipeline Flow Diverter Treatment of Posterior Communicating Artery Aneurysms

Litao, Miguel S; Burkhardt, Jan-Karl; Tanweer, Omar; Raz, Eytan; Huang, Paul; Becske, Tibor; Shapiro, Maksim; Riina, Howard; Nelson, Peter K
INTRODUCTION/BACKGROUND:Flow diverters such as the pipeline embolization device (PED) cause hemodynamic changes of the treated vessel segment. In posterior communicating artery (PcomA), aneurysms' unique anatomic consideration have to be taken in account due to the connection between the anterior and posterior circulation. We hypothesize that in conjunction with PcomA remodeling, there will also be remodeling of the ipsilateral P1 segment of the posterior cerebral artery (PCA) after PED treatment for PcomA aneurysms. METHODS:We retrospectively collected radiological as well as clinical data of PcomA aneurysm patients treated with PED including PcomA and P1 vessel diameters before and after treatment as well as patient and aneurysm characteristics. RESULTS:= 0.042). There were no neurologic complications on LFU. CONCLUSION/CONCLUSIONS:In the treatment of PcomA aneurysms with PED, the P1 segment of the PCA increases in diameter while the PcomA diameter decreases. Our results suggest that this remodeling effect is associated with aneurysm occlusion and decrease of PcomA is hemodynamically compensated for by an increase in the ipsilateral P1 diameter.
PMCID:8162531
PMID: 34066972
ISSN: 2035-8385
CID: 4891352

Large Subcortical Intracerebral Hemorrhage Because of Reversible Cerebral Vasoconstriction Syndrome: A Case Study

Allen, Alexander; Raz, Eytan; Huang, Paul; Rostanski, Sara K
PMID: 32867598
ISSN: 1524-4628
CID: 4582912

Radiosurgery for Unruptured Intervention - Naïve Pediatric Brain Arteriovenous Malformations

Chen, Ching-Jen; Lee, Cheng-Chia; Kano, Hideyuki; Kearns, Kathryn N; Ding, Dale; Tzeng, Shih-Wei; Atik, Ahmet Fatih; Joshi, Krishna; Huang, Paul P; Kondziolka, Douglas; Ironside, Natasha; Mathieu, David; Iorio-Morin, Christian; Grills, Inga S; Quinn, Thomas J; Siddiqui, Zaid A; Marvin, Kim; Feliciano, Caleb; Starke, Robert M; Faramand, Andrew; Barnett, Gene; Lunsford, L Dade; Sheehan, Jason P
BACKGROUND:Long-term data regarding stereotactic radiosurgery (SRS) as a standalone therapy for unruptured pediatric brain arteriovenous malformations (AVMs) are incompletely defined. OBJECTIVE:To evaluate, in a multicenter, retrospective cohort study, the outcomes after SRS for unruptured, intervention-naïve pediatric AVMs. METHODS:To retrospectively analyze the International Radiosurgery Research Foundation pediatric AVM database from 1987 to 2018. Pediatric patients with unruptured, previously untreated AVMs who underwent SRS were included. The primary endpoint was a composite of hemorrhagic stroke, death, or permanently symptomatic radiation-induced changes. RESULTS:The study cohort comprised 101 patients (mean follow-up 80.8 mo). The primary endpoint occurred in 14%, comprising hemorrhagic stroke, death, and permanent radiation-induced changes in 6%, 3%, and 8%, respectively. Estimated probabilities of the primary endpoint were 5.2%, 10.8%, and 23.0% at 2, 5, and 10 yr, respectively. Estimated probabilities of AVM obliteration at 5 and 10 yr were 64% and 82%, respectively. Single SRS treatment (P = .007) and higher margin dose (P = .005) were predictors of obliteration. Subgroup analysis of Spetzler-Martin grade I-III AVMs estimated primary endpoint probabilities of 3.7%, 8.4%, and 18.7% at 2, 5, and 10 yr, respectively. CONCLUSION/CONCLUSIONS:Treatment of unruptured, intervention-naïve AVMs in the pediatric population with SRS carries an approximately 2% annual risk of morbidity and mortality, which appears to plateau after 10 yr. The poorly described natural history of pediatric AVMs renders any comparison of SRS vs conservative management imperfect.
PMID: 31942635
ISSN: 1524-4040
CID: 4264502

Early obliteration of pediatric brain arteriovenous malformations after stereotactic radiosurgery: an international multicenter study

Burke, Rebecca M; Chen, Ching-Jen; Ding, Dale; Buell, Thomas J; Sokolowski, Jennifer D; Lee, Cheng-Chia; Kano, Hideyuki; Kearns, Kathryn N; Tzeng, Shih-Wei; Yang, Huai-Che; Huang, Paul P; Kondziolka, Douglas; Ironside, Natasha; Mathieu, David; Iorio-Morin, Christian; Grills, Inga S; Feliciano, Caleb; Barnett, Gene H; Starke, Robert M; Lunsford, L Dade; Sheehan, Jason P
OBJECTIVE:Stereotactic radiosurgery (SRS) is a treatment option for pediatric brain arteriovenous malformations (AVMs), and early obliteration could encourage SRS utilization for a subset of particularly radiosensitive lesions. The objective of this study was to determine predictors of early obliteration after SRS for pediatric AVMs. METHODS:The authors performed a retrospective review of the International Radiosurgery Research Foundation AVM database. Obliterated pediatric AVMs were sorted into early (obliteration ≤ 24 months after SRS) and late (obliteration > 24 months after SRS) responders. Predictors of early obliteration were identified, and the outcomes of each group were compared. RESULTS:The overall study cohort was composed of 345 pediatric patients with obliterated AVMs. The early and late obliteration cohorts were made up of 95 (28%) and 250 (72%) patients, respectively. Independent predictors of early obliteration were female sex, a single SRS treatment, a higher margin dose, a higher isodose line, a deep AVM location, and a smaller AVM volume. The crude rate of post-SRS hemorrhage was 50% lower in the early (3.2%) than in the late (6.4%) obliteration cohorts, but this difference was not statistically significant (p = 0.248). The other outcomes of the early versus late obliteration cohorts were similar, with respect to symptomatic radiation-induced changes (RICs), cyst formation, and tumor formation. CONCLUSIONS:Approximately one-quarter of pediatric AVMs that become obliterated after SRS will achieve this radiological endpoint within 24 months of initial SRS. The authors identified multiple factors associated with early obliteration, which may aid in prognostication and management. The overall risks of delayed hemorrhage, RICs, cyst formation, and tumor formation were not statistically different in patients with early versus late obliteration.
PMID: 32590353
ISSN: 1933-0715
CID: 4516752

Early Anti-Xa Assay-Guided Low Molecular Weight Heparin Chemoprophylaxis Is Safe in Adult Patients with Acute Traumatic Brain Injury

Rodier, Simon G; Kim, Mirhee; Moore, Samantha; Frangos, Spiros G; Tandon, Manish; Klein, Michael J; Berry, Cherisse D; Huang, Paul P; DiMaggio, Charles J; Bukur, Marko
This study evaluated the safety of early anti-factor Xa assay-guided enoxaparin dosing for chemoprophylaxis in patients with TBI. We hypothesized that assay-guided chemoprophylaxis would be comparable in the risk of intracranial hemorrhage (ICH) progression to fixed dosing. An observational analysis of adult patients with blunt traumatic brain injury (TBI) was performed at a Level I trauma center from August 2016 to September 2017. Patients in the assay-guided group were treated with an initial enoxaparin dose of 0.5 mg/kg, with peak anti-factor Xa activity measured four hours after the third dose. Prophylactic range was defined as 0.2 to 0.5 IU/mL with a dose adjustment of ± 10 mg based on the assay result. The assay-guided group was compared with historical fixed-dose controls and to a TBI cohort from the most recent Trauma Quality Improvement Project dataset. Of 179 patients included in the study, 85 were in the assay-guided group and 94 were in the fixed-dose group. Compared with the fixed-dose group, the assay-guided group had a lower Glasgow Coma Score and higher Injury Severity Score. The proportion of severe (Abbreviated Injury Score, head ≥3) TBI, ICH progression, and venous thromboembolism rates were similar between all groups. The assay-guided and fixed-dose groups had chemoprophylaxis initiated earlier than the Trauma Quality Improvement Project group. The assay-guided group had the highest percentage of low molecular weight heparin use. Early initiation of enoxaparin anti-factor Xa assay-guided venous thromboembolism chemoprophylaxis has a comparable risk of ICH progression to fixed dosing in patients with TBI. These findings should be validated prospectively in a multicenter study.
PMID: 32391762
ISSN: 1555-9823
CID: 4430962

Stereotactic radiosurgery for pediatric brain arteriovenous malformations: long-term outcomes

Chen, Ching-Jen; Lee, Cheng-Chia; Kano, Hideyuki; Kearns, Kathryn N; Ding, Dale; Tzeng, Shih-Wei; Atik, Ahmet; Joshi, Krishna; Barnett, Gene H; Huang, Paul P; Kondziolka, Douglas; Mathieu, David; Iorio-Morin, Christian; Grills, Inga S; Quinn, Thomas J; Siddiqui, Zaid A; Marvin, Kim; Feliciano, Caleb; Faramand, Andrew; Lunsford, L Dade; Sheehan, Jason P
OBJECTIVE:Contrary to the better described obliteration- and hemorrhage-related data after stereotactic radiosurgery (SRS) of brain arteriovenous malformations (AVMs) in pediatric patients, estimates of the rarer complications, including cyst and tumor formation, are limited in the literature. The aim of the present study was to assess the long-term outcomes and risks of SRS for AVMs in pediatric patients (age < 18 years). METHODS:The authors retrospectively analyzed the International Radiosurgery Research Foundation pediatric AVM database for the years 1987 to 2018. AVM obliteration, post-SRS hemorrhage, cyst formation, and tumor formation were assessed. Cumulative probabilities, adjusted for the competing risk of death, were calculated. RESULTS:The study cohort comprised 539 pediatric AVM patients (mean follow-up 85.8 months). AVM obliteration was observed in 64.3% of patients, with cumulative probabilities of 63.6% (95% CI 58.8%-68.0%), 77.1% (95% CI 72.1%-81.3%), and 88.1% (95% CI 82.5%-92.0%) over 5, 10, and 15 years, respectively. Post-SRS hemorrhage was observed in 8.4% of patients, with cumulative probabilities of 4.9% (95% CI 3.1%-7.2%), 9.7% (95% CI 6.4%-13.7%), and 14.5% (95% CI 9.5%-20.5%) over 5, 10, and 15 years, respectively. Cyst formation was observed in 2.1% of patients, with cumulative probabilities of 5.5% (95% CI 2.3%-10.7%) and 6.9% (95% CI 3.1%-12.9%) over 10 and 15 years, respectively. Meningiomas were observed in 2 patients (0.4%) at 10 and 12 years after SRS, with a cumulative probability of 3.1% (95% CI 0.6%-9.7%) over 15 years. CONCLUSIONS:AVM obliteration can be expected after SRS in the majority of the pediatric population, with a relatively low risk of hemorrhage during the latency period. Cyst and benign tumor formation after SRS can be observed in 7% and 3% of patients over 15 years, respectively. Longitudinal surveillance for delayed neoplasia is prudent despite its low incidence.
PMID: 32032957
ISSN: 1933-0715
CID: 4301582

Early Anti-Xa Assay-Guided Low Molecular Weight Heparin Prophylaxis Is Safe in Adult Patients with Acute Traumatic Brain Injury [Meeting Abstract]

Rodier, S; Kim, M; Moore, S; Frangos, S; Tandon, M; Klein, M; Berry, C D; Huang, P P; DiMaggio, C; Bukur, M
Introduction: Venous thromboembolism (VTE) represents a significant source of morbidity after traumatic brain injury (TBI). The safety and timing of VTE chemoprophylaxis after TBI remain a concern, given the risk of intracranial hemorrhage progression. We evaluated the safety of anti-factor Xa assay-guided dosing for chemoprophylaxis in adult TBI patients. We hypothesized that Xa assay-guided chemoprophylaxis would be safe compared with fixed-dosing.
Method(s): An observational analysis of adult TBI patients was performed at a Level I trauma center from August 2016 to September 2017. Patients in the assay-guided group received an initial enoxaparin dose of 0.5 mg/kg, with peak anti-factor Xa activity measured 4 hours after the third dose. Prophylactic range was defined as 0.2 to 0.5 IU/mL with dose adjustment of +/-10 mg based on the assay result. The assay-guided group compared with historical fixed-dose controls, and a TBI cohort from the most recent Trauma Quality Improvement Program data set.
Result(s): Of the 179 patients included in the study, 85 patients were in the assay-guided group and 94 were in the fixed-dose group. Relative to the fixed-dose group, the assay-guided group had a lower Glasgow Coma Scale score and higher Injury Severity Score (Table). The proportion of severe (Abbreviated Injury Scale head >=4) TBI, intracranial hemorrhage progression, and VTE rates were similar between groups. However, the assay-guided group had chemoprophylaxis initiated earlier and had a higher percentage of low molecular weight heparin use relative to the Trauma Quality Improvement Program sample.
Conclusion(s): Early initiation of low molecular weight heparin anti-factor Xa assay-guided VTE prophylaxis is safe in TBI patients. These findings should be validated prospectively in a multicenter study. [Figure presented]
Copyright
EMBASE:2002921623
ISSN: 1072-7515
CID: 4109112

Stereotactic Radiosurgery for Unruptured Versus Ruptured Pediatric Brain Arteriovenous Malformations

Chen, Ching-Jen; Lee, Cheng-Chia; Ding, Dale; Tzeng, Shih-Wei; Kearns, Kathryn N; Kano, Hideyuki; Atik, Ahmet; Ironside, Natasha; Joshi, Krishna; Huang, Paul P; Kondziolka, Douglas; Mathieu, David; Iorio-Morin, Christian; Grills, Inga S; Quinn, Thomas J; Siddiqui, Zaid; Marvin, Kim; Feliciano, Caleb; Faramand, Andrew; Starke, Robert M; Barnett, Gene; Lunsford, L Dade; Sheehan, Jason P
Background and Purpose- The effects of prior hemorrhage on stereotactic radiosurgery (SRS) outcomes for pediatric arteriovenous malformations (AVMs) are not well defined. The aim of this multicenter, retrospective cohort study is to compare the SRS outcomes for unruptured versus ruptured pediatric AVMs. Methods- The International Radiosurgery Research Foundation pediatric AVM database from 1987 to 2018 was reviewed retrospectively. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes. Associations between prior hemorrhage and outcomes were adjusted for baseline differences, inverse probability weights, and competing risks. Results- The study cohort comprised 153 unruptured and 386 ruptured AVMs. Favorable outcome was achieved in 48.4% and 60.4% of unruptured and ruptured AVMs, respectively (adjusted odds ratio, 1.353; P=0.190). Cumulative AVM obliteration probabilities were 51.2%, 59.4%, 64.2%, and 70.0% for unruptured and 61.0%, 69.3%, 74.0%, and 79.3% for ruptured AVMs at 4, 6, 8, and 10 years, respectively (subhazard ratio, 1.311; P=0.020). Cumulative post-SRS hemorrhage probabilities were 4.5%, 5.6%, 5.6%, and 9.8% for unruptured and 4.7%, 6.1%, 6.1%, and 10.6% for ruptured AVMs at 4, 6, 8, and 10 years, respectively (subhazard ratio, 1.086; P=0.825). Probabilities of AVM obliteration (adjusted subhazard ratio, 0.968; P=0.850) and post-SRS hemorrhage (adjusted subhazard ratio, 1.663; P=0.251) were comparable between the 2 cohorts after inverse probability weight adjustments. Symptomatic (15.8% versus 8.1%; adjusted odds ratio, 0.400; P=0.008) and permanent (9.2% versus 5.0%; adjusted odds ratio, 0.441; P=0.045) radiation-induced change were more common in unruptured AVMs. Conclusions- The overall outcomes after SRS for unruptured versus ruptured pediatric AVMs are comparable. However, symptomatic and permanent radiation-induced change occur more frequently in pediatric patients with unruptured AVMs.
PMID: 31387513
ISSN: 1524-4628
CID: 4034312

Endovascular and Microsurgical Aneurysm Training in a Chicken Thigh and Leg Pulsatile Model

Tanweer, Omar; Mureb, Monica C; Pacione, Donato; Sen, Rajeev; Jafar, Jafar J; Riina, Howard A; Huang, Paul P
BACKGROUND:Neurovascular training models include animal models, synthetics, or computer simulation. In vivo models are expensive and require significant resources. Synthetic/computer models do not reflect the elasticity of fresh vessels. We describe an endovascular and microsurgical training model using a chicken thigh/leg. METHODS:20 chicken thigh/leg models were obtained. Angiography was utilized to understand the anatomy. Proximal cannulation with a 5-French catheter was achieved and connected to a hemostatic valve with a pump to simulate pulsatile flow. Aneurysms were created at the thigh-leg junction. For clipping training, 3 types of aneurysms were created to reproduce anatomy seen in middle cerebral, anterior communicating and posterior communicating aneurysms. RESULTS:The average cost per specimen from was $1.70 ± 0.30. The diameter of the proximal femoral artery (PFA) was 2.4 mm ± 0.2 mm. The length from the PFA to the aneurysm was 9.5 cm ± 0.7 cm. Distal catheterization was successful in all cases (n=6). Successful deployment of coils and a stent was achieved under fluoroscopic guidance. Gross over-sizing of coils and other mistakes led to aneurysm rupture. Each examiner performed an exploration of the pulsatile aneurysm, application and reapplication of a variety of clips and then final inspection of branching vessels to confirm patency. CONCLUSIONS:The chicken thigh/leg model provides training opportunities in microsurgical suturing, endovascular techniques for aneurysm obliteration, and microsurgical reconstruction of aneurysms. It combines affordability, time efficiency and reproducibility. Further studies measuring improvement in technical aneurysm management and comparison to other training models are warranted.
PMID: 30641239
ISSN: 1878-8769
CID: 3595192