Stereotactic Radiosurgery for Unruptured Versus Ruptured Pediatric Brain Arteriovenous Malformations.

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.

Nature or nurture: a latent ossification of the posterior longitudinal ligament after atlantoaxial fusion. Illustrative case.

BACKGROUND: The natural history of ossification of the posterior longitudinal ligament (OPLL) remains poorly understood and multiple etiologies have been reported. However, most have focused on the characteristics of the patient rather than alternation of mechanical stress after spinal fusion. OBSERVATIONS: This report describes, for the first time, a de novo OPLL found at the subaxial cervical spine 7 years after an atlantoaxial fusion surgery. A 57-year-old female initially required atlantoaxial arthrodesis for os odontoideum and stenosis that caused myelopathy. The posterior fusion surgery went smoothly without complications and the patient had good recovery of neurological functions. There was no associated instability, trauma, or reoperations during the follow-up. Seven years later, the patient presented with slight neck pain and a newly developed OPLL at C3-4 caudal to the C1-2 fusion construct. LESSONS: Conflicting with the conventional concept that OPLL is common in elderly men with genetic or hormonal factors, or associated spondyloarthropathies, OPLL could develop in women even after solid C1-2 fusion. The adjacent subaxial cervical spine is not free of risks for subsequent development of OPLL and cervical spondylotic myelopathy. This case illustration extends the scope of etiologies of OPLL within the present literature.

Herniated disc of lumbar spine caused by bone cement leakage after kyphoplasty - A case report and literature review.

INTRODUCTION AND IMPORTANCE: To describe an unusual case with herniated disc caused by bone cement leaking to disc space after kyphoplasty. CASE PRESENTATION: We reported a 72-year-old woman with L4 osteoporotic compression fracture. New-onset of left sciatica, numbness and intermittent claudication suffered her immediate after kyphoplasty. Herniated disc caused by bone cement leaking to disc space after kyphoplasty. The patient was post decompressive operation of L34 and the symptoms subsided well then. CLINICAL DISCUSSION: Percutaneous vertebroplasty (PVP) was a common procedure today. Especially to back pain caused by osteoporotic fracture, reported pain relief rate was satisfactory. Current studies about bone cement leakage showed kyphoplasty less than vertebroplasty. However, for the mechanism and stress effect of balloon expansion, new weak points and cracks over endplate was created, which may cause bone cement leakage to disc space and related symptoms. CONCLUSION: Kyphoplasty was a common, effective and minimal invasive operation for patients with compression fracture of spine. Cement leakage to intervertebral disc space was generally asymptomatic, but it should be avoided as much as possible. The leakage could affect the stability and weight-bearing of spinal column. Accelerated degenerative process of disc would be found and newly herniated disc would be noted. It should be ceased the procedure when relative amount of bone cement leakage to disc space during kyphoplasty.

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

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.

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

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.

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

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.

Radiosurgery for Unruptured Intervention-Naïve Pediatric Brain Arteriovenous Malformations.

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: 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.

KinasePhos: a web tool for identifying protein kinase-specific phosphorylation sites.

KinasePhos is a novel web server for computationally identifying catalytic kinase-specific phosphorylation sites. The known phosphorylation sites from public domain data sources are categorized by their annotated protein kinases. Based on the profile hidden Markov model, computational models are learned from the kinase-specific groups of the phosphorylation sites. After evaluating the learned models, the model with highest accuracy was selected from each kinase-specific group, for use in a web-based prediction tool for identifying protein phosphorylation sites. Therefore, this work developed a kinase-specific phosphorylation site prediction tool with both high sensitivity and specificity. The prediction tool is freely available at http://KinasePhos.mbc.nctu.edu.tw/.

Incorporating hidden Markov models for identifying protein kinase-specific phosphorylation sites.

Protein phosphorylation, which is an important mechanism in posttranslational modification, affects essential cellular processes such as metabolism, cell signaling, differentiation, and membrane transportation. Proteins are phosphorylated by a variety of protein kinases. In this investigation, we develop a novel tool to computationally predict catalytic kinase-specific phosphorylation sites. The known phosphorylation sites from public domain data sources are categorized by their annotated protein kinases. Based on the concepts of profile Hidden Markov Models (HMM), computational models are trained from the kinase-specific groups of phosphorylation sites. After evaluating the trained models, we select the model with highest accuracy in each kinase-specific group and provide a Web-based prediction tool for identifying protein phosphorylation sites. The main contribution here is that we have developed a kinase-specific phosphorylation site prediction tool with both high sensitivity and specificity.