Biosensors with left ventricular assist devices.

Heart failure imposes a significant global health burden, standing as a primary contributor to mortality. Various indicators and physiological shifts within the body may hint at distinct cardiac conditions. Specific biosensors have the capability to identify these changes. Integrating or embedding these biosensors into mechanical circulatory support devices (MCSDs), such as left ventricular assist devices (LVADs), becomes crucial for monitoring alterations in biochemical and physiological factors subsequent to an MCSD implantation. Detecting abnormal changes early in the course of disease progression will allow for improved patient outcomes and prognosis following an MCSD implantation. The aim of this review is to explore the available biosensors that may be coupled or implanted alongside LVADs to monitor biomarkers and changes in physiological parameters. Different fabrication materials for the biosensors are discussed, including their advantages and disadvantages. This review also examines the feasibility of integrating feedback control mechanisms into LVAD systems using data from the biosensors. Challenges facing this emerging technology and future directions for research and development are outlined as well. The overarching goal is to provide an overview of how implanted biosensors may improve the performance and outcomes of LVADs through continuous monitoring and closed-loop control.

Cardiovascular Disease and COVID-19 Vaccines: A Systematic Review and Analysis of Published Cases.

As vaccination against COVID-19 became more widespread, side-effects that were not initially detected during clinical trials became more prominent. The aim of this systematic review is to discuss reports of adverse cardiovascular events associated with COVID-19 vaccination. Databases were searched from inception up to August 2022 to identify case reports and case series reporting on patients with cardiovascular disease after COVID-19 vaccination. This study assessed 150 published cases. Of these, 109 were case reports and 41 were case series. The majority of patients were male (n=302, 86.6%), with a mean age of 27.6 ± 16.7 years. Of the included patients, 268 (76.6%) had myocarditis, 50 (14.6%) had myopericarditis, 8 (2.3%) had pericarditis, and only 4 (1.1%) had stress-induced cardiomyopathy. Moreover, 30 (8.6%) and 11 (3.1%) were diagnosed with arrhythmia and ischaemic heart disease, respectively. Ultimately, cardiovascular complications after COVID-19 vaccination include myocarditis, myopericarditis, ischaemic heart disease and arrhythmia. The young population, especially young male patients, could be more vulnerable to myocarditis.

Stereotactic Radiosurgery for Trigeminal Neuralgia in Patients With Multiple Sclerosis: A Multicenter Study.

BACKGROUND: Facial pain response (PR) to various surgical interventions in patients with multiple sclerosis (MS)-related trigeminal neuralgia (TN) is much less optimal. No large patient series regarding stereotactic radiosurgery (SRS) has been published. OBJECTIVE: To evaluate the clinical outcomes of MS-related TN treated with SRS. METHODS: This is a retrospective cohort study. A total of 263 patients contributed by 9 member tertiary referral Gamma Knife centers (2 in Canada and 7 in USA) of the International Gamma Knife Research Consortium (IGKRF) constituted this study. RESULTS: The median latency period of PR after SRS was 1 mo. Reasonable pain control (Barrow Neurological Institute [BNI] Pain Scores I-IIIb) was achieved in 232 patients (88.2%). The median maintenance period from SRS was 14.1 months (range, 10 days to 10 years). The actuarial reasonable pain control maintenance rates at 1 yr, 2 yr, and 4 yr were 54%, 35%, and 24%, respectively. There was a correlation between the status of achieving BNI-I and the maintenance of facial pain recurrence-free rate. The median recurrence-free rate was 36 mo and 12.2 mo in patients achieving BNI-I and BNI > I, respectively (P = .046). Among 210 patients with known status of post-SRS complications, the new-onset of facial numbness (BNI-I or II) after SRS occurred in 21 patients (10%). CONCLUSION: In this largest series SRS offers a reasonable benefit to risk profile for patients who have exhausted medical management. More favorable initial response to SRS may predict a long-lasting pain control.

Socioeconomic restraints and brain tumor surgery in low-income countries.

Healthcare spending has become a grave concern to national budgets worldwide, and to a greater extent in low-income countries. Brain tumors are a serious disease that affects a significant percentage of the population, and thus proper allocation of healthcare provisions for these patients to achieve acceptable outcomes is a must. The authors reviewed patients undergoing craniotomy for tumor resection at their institution for the preceding 3 months. All the methods used for preoperative planning, intraoperative management, and postoperative care of these patients were documented. Compromises to limit spending were made at each stage to limit expenditure, including low-resolution MRI, sparse use of intraoperative monitoring and image guidance, and lack of dedicated postoperative neurocritical ICU. This study included a cohort of 193 patients. The average cost from diagnosis to discharge was $1795 per patient (costs are expressed in USD). On average, there was a mortality rate of 10.5% and a neurological morbidity rate of 14%, of whom only 82.2% improved on discharge or at follow-up. The average length of stay at the hospital for these patients was 9.09 days, with a surgical site infection rate of only 3.5%. The authors believe that despite the great number of financial limitations facing neurosurgical practice in low-income countries, surgery can still be performed with reasonable outcomes.

Outcome of single-trajectory rigid endoscopic third ventriculostomy and biopsy in the management algorithm of pineal region tumors: a case series and review of the literature.

BACKGROUND: Tumors within the pineal region represent 1.5 to 8.5% of the pediatric brain tumors and 1.2% of all brain tumors. A management algorithm has been proposed in several publications. The algorithm includes endoscopic third ventriculostomy (ETV) and biopsy in cases presenting with hydrocephalus. In this series, we are presenting the efficacy of a single-trajectory approach for both ETV and biopsy. METHODS: Eleven cases were admitted to Alexandria main university hospital from 2013 to 2016 presenting with pineal region tumors and hydrocephalus. Mean age at diagnosis was 11 years (1-27 years). All cases had ETV and biopsy using rigid ventriculoscope through a single trajectory from a burr hole planned on preoperative imaging. Follow-up period was 7-48 months. RESULTS: All 11 cases presented with hydrocephalus and increased intracranial pressure manifestations. Histopathological diagnosis was successful in 9 out of 11 cases (81.8%). Three cases were germ-cell tumors, two cases were pineoblastomas, two cases were pilocytic astrocytomas, and two cases were grade 2 tectal gliomas. Five of the ETV cases (45.5%) failed and required VPS later on. Other complications of ETV included one case of intraventricular hemorrhage and a case with tumor disseminated to the basal cisterns. CONCLUSION: In our series, we were able to achieve ETV and biopsy through a single trajectory and a rigid endoscope with results comparable to other studies in the literature.

Effect of treatment period on outcomes after stereotactic radiosurgery for brain arteriovenous malformations: an international multicenter study.

OBJECTIVEThe role of and technique for stereotactic radiosurgery (SRS) in the management of arteriovenous malformations (AVMs) have evolved over the past four decades. The aim of this multicenter, retrospective cohort study was to compare the SRS outcomes of AVMs treated during different time periods.METHODSThe authors selected patients with AVMs who underwent single-session SRS at 8 different centers from 1988 to 2014 with follow-up ≥ 6 months. The SRS eras were categorized as early (1988-2000) or modern (2001-2014). Statistical analyses were performed to compare the baseline characteristics and outcomes of the early versus modern SRS eras. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RICs).RESULTSThe study cohort comprised 2248 patients with AVMs, including 1584 in the early and 664 in the modern SRS eras. AVMs in the early SRS era were significantly smaller (p < 0.001 for maximum diameter and volume), and they were treated with a significantly higher radiosurgical margin dose (p < 0.001). The obliteration rate was significantly higher in the early SRS era (65% vs 51%, p < 0.001), and earlier SRS treatment period was an independent predictor of obliteration in the multivariate analysis (p < 0.001). The rates of post-SRS hemorrhage and radiological, symptomatic, and permanent RICs were not significantly different between the two groups. Favorable outcome was achieved in a significantly higher proportion of patients in the early SRS era (61% vs 45%, p < 0.001), but the earlier SRS era was not statistically significant in the multivariate analysis (p = 0.470) with favorable outcome.CONCLUSIONSDespite considerable advances in SRS technology, refinement of AVM selection, and contemporary multimodality AVM treatment, the study failed to observe substantial improvements in SRS favorable outcomes or obliteration for patients with AVMs over time. Differences in baseline AVM characteristics and SRS treatment parameters may partially account for the significantly lower obliteration rates in the modern SRS era. However, improvements in patient selection and dose planning are necessary to optimize the utility of SRS in the contemporary management of AVMs.

Impact of 2-staged stereotactic radiosurgery for treatment of brain metastases ≥ 2 cm.

OBJECTIVE Stereotactic radiosurgery (SRS) is the primary modality for treating brain metastases. However, effective radiosurgical control of brain metastases ≥ 2 cm in maximum diameter remains challenging and is associated with suboptimal local control (LC) rates of 37%-62% and an increased risk of treatment-related toxicity. To enhance LC while limiting adverse effects (AEs) of radiation in these patients, a dose-dense treatment regimen using 2-staged SRS (2-SSRS) was used. The objective of this study was to evaluate the efficacy and toxicity of this treatment strategy. METHODS Fifty-four patients (with 63 brain metastases ≥ 2 cm) treated with 2-SSRS were evaluated as part of an institutional review board-approved retrospective review. Volumetric measurements at first-stage stereotactic radiosurgery (first SSRS) and second-stage SRS (second SSRS) treatments and on follow-up imaging studies were determined. In addition to patient demographic data and tumor characteristics, the study evaluated 3 primary outcomes: 1) response at first follow-up MRI, 2) time to local progression (TTP), and 3) overall survival (OS) with 2-SSRS. Response was analyzed using methods for binary data, TTP was analyzed using competing-risks methods to account for patients who died without disease progression, and OS was analyzed using conventional time-to-event methods. When needed, analyses accounted for multiple lesions in the same patient. RESULTS Among 54 patients, 46 (85%) had 1 brain metastasis treated with 2-SSRS, 7 patients (13%) had 2 brain metastases concurrently treated with 2-SSRS, and 1 patient underwent 2-SSRS for 3 concurrent brain metastases ≥ 2 cm. The median age was 63 years (range 23-83 years), 23 patients (43%) had non-small cell lung cancer, and 14 patients (26%) had radioresistant tumors (renal or melanoma). The median doses at first and second SSRS were 15 Gy (range 12-18 Gy) and 15 Gy (range 12-15 Gy), respectively. The median duration between stages was 34 days, and median tumor volumes at the first and second SSRS were 10.5 cm3 (range 2.4-31.3 cm3) and 7.0 cm3 (range 1.0-29.7 cm3). Three-month follow-up imaging results were available for 43 lesions; the median volume was 4.0 cm3 (range 0.1-23.1 cm3). The median change in volume compared with baseline was a decrease of 54.9% (range -98.2% to 66.1%; p < 0.001). Overall, 9 lesions (14.3%) demonstrated local progression, with a median of 5.2 months (range 1.3-7.4 months), and 7 (11.1%) demonstrated AEs (6.4% Grade 1 and 2 toxicity; 4.8% Grade 3). The estimated cumulative incidence of local progression at 6 months was 12% ± 4%, corresponding to an LC rate of 88%. Shorter TTP was associated with greater tumor volume at baseline (p = 0.01) and smaller absolute (p = 0.006) and relative (p = 0.05) decreases in tumor volume from baseline to second SSRS. Estimated OS rates at 6 and 12 months were 65% ± 7% and 49% ± 8%, respectively. CONCLUSIONS 2-SSRS is an effective treatment modality that resulted in significant reduction of brain metastases ≥ 2 cm, with excellent 3-month (95%) and 6-month (88%) LC rates and an overall AE rate of 11%. Prospective studies with larger cohorts and longer follow-up are necessary to assess the durability and toxicities of 2-SSRS.

Stereotactic radiosurgery for Spetzler-Martin Grade IV and V arteriovenous malformations: an international multicenter study.

OBJECTIVE Due to the complexity of Spetzler-Martin (SM) Grade IV-V arteriovenous malformations (AVMs), the management of these lesions remains controversial. The aims of this multicenter, retrospective cohort study were to evaluate the outcomes after single-session stereotactic radiosurgery (SRS) for SM Grade IV-V AVMs and determine predictive factors. METHODS The authors retrospectively pooled data from 233 patients (mean age 33 years) with SM Grade IV (94.4%) or V AVMs (5.6%) treated with single-session SRS at 8 participating centers in the International Gamma Knife Research Foundation. Pre-SRS embolization was performed in 71 AVMs (30.5%). The mean nidus volume, SRS margin dose, and follow-up duration were 9.7 cm3, 17.3 Gy, and 84.5 months, respectively. Statistical analyses were performed to identify factors associated with post-SRS outcomes. RESULTS At a mean follow-up interval of 84.5 months, favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RIC) and was achieved in 26.2% of patients. The actuarial obliteration rates at 3, 7, 10, and 12 years were 15%, 34%, 37%, and 42%, respectively. The annual post-SRS hemorrhage rate was 3.0%. Symptomatic and permanent RIC occurred in 10.7% and 4% of the patients, respectively. Only larger AVM diameter (p = 0.04) was found to be an independent predictor of unfavorable outcome in the multivariate logistic regression analysis. The rate of favorable outcome was significantly lower for unruptured SM Grade IV-V AVMs compared with ruptured ones (p = 0.042). Prior embolization was a negative independent predictor of AVM obliteration (p = 0.024) and radiologically evident RIC (p = 0.05) in the respective multivariate analyses. CONCLUSIONS In this multi-institutional study, single-session SRS had limited efficacy in the management of SM Grade IV-V AVMs. Favorable outcome was only achieved in a minority of unruptured SM Grade IV-V AVMs, which supports less frequent utilization of SRS for the management of these lesions. A volume-staged SRS approach for large AVMs represents an alternative approach for high-grade AVMs, but it requires further investigation.

Stereotactic radiosurgery for jugular foramen schwannomas: an international multicenter study.

OBJECTIVE: For some jugular foramen schwannomas (JFSs), complete resection is possible but may be associated with significant morbidity. Stereotactic radiosurgery (SRS) is a minimally invasive alternative or adjunct to microsurgery for JFSs. The authors reviewed clinical and imaging outcomes of SRS for patients with these tumors. METHODS: Nine participating centers of the International Gamma Knife Research Foundation identified 92 patients who underwent SRS between 1990 and 2013. Forty-one patients had prior subtotal microsurgical resection. The median interval between previous surgery and SRS was 15 months (range 0.5-144 months). Eighty-four patients had preexisting cranial nerve (CN) symptoms and signs. The median tumor volume was 4.1 cm3 (range 0.8-22.6 cm3), and the median margin dose was 12.5 Gy (range 10-18 Gy). Patients with neurofibromatosis were excluded from this study. RESULTS: The median follow-up was 51 months (range 6-266 months). Tumors regressed in 47 patients, remained stable in 33, and progressed in 12. The progression-free survival (PFS) was 93% at 3 years, 87% at 5 years, and 82% at 10 years. In the entire series, only a dumbbell shape (extension extracranially via the jugular foramen) was significantly associated with worse PFS. In the group of patients without prior microsurgery (n = 51), factors associated with better PFS included tumor volume < 6 cm3 (p = 0.037) and non-dumbbell-shaped tumors (p = 0.015). Preexisting cranial neuropathies improved in 27 patients, remained stable in 51, and worsened in 14. The CN function improved after SRS in 12% of patients at 1 year, 24% at 2 years, 27% at 3 years, and 32% at 5 years. Symptomatic adverse radiation effects occurred in 7 patients at a median of 7 months after SRS (range 5-38 months). Six patients underwent repeat SRS at a median of 64 months (range 44-134 months). Four patients underwent resection at a median of 14 months after SRS (range 8-30 months). CONCLUSIONS: Stereotactic radiosurgery proved to be a safe and effective primary or adjuvant management approach for JFSs. Long-term tumor control rates and stability or improvement in CN function were confirmed.

Phase I Trial of Radiosurgery Dose Escalation Plus Bevacizumab in Patients With Recurrent/Progressive Glioblastoma.

BACKGROUND: The effectiveness of stereotactic radiosurgery (SRS) for recurrent glioblastoma (rGBM) remains uncertain. SRS has been associated with a high risk of radionecrosis in gliomas. OBJECTIVE: To determine the safety of dose escalation of single-fraction radiosurgery for rGBM in the setting of bevacizumab therapy. METHODS: We conducted a prospective trial to determine the safety and synergistic benefit of higher doses of SRS administered with bevacizumab for rGBM. A single dose of bevacizumab was given prior to SRS and continued until progression. Dose-limiting toxicity was evaluated in successive cohorts of 3 patients. RESULTS: Seven males and 2 females entered the study. The maximum linear diameter of the enhancing tumor was 2.58 cm (2.04-3.09). Prescription dose was escalated from 18 to 22 Gy. The radiosurgery target was chosen before the first dose of bevacizumab, about 1 wk prior to SRS treatment. Pre-SRS bevacizumab treatment was associated with a reduction of the mean volume of the enhancing lesion from 4.7 to 2.86 cm3 on the day of SRS (P = .103). No patient developed an acute side effect related to SRS treatment. The combination of SRS and bevacizumab resulted in a partial response in 3 patients and stable disease in 6 patients. Median progression-free and overall survival were 7.5 and 13 mo, respectively. CONCLUSION: A single dose of bevacizumab prior to SRS permitted safe prescription dose escalation up to 22 Gy for rGBM. Further evaluation of the efficacy of SRS for rGBM should be performed in the setting of bevacizumab treatment.

Radiosurgery for Unruptured Brain Arteriovenous Malformations: An International Multicenter Retrospective Cohort Study.

BACKGROUND: The role of intervention in the management of unruptured brain arteriovenous malformations (AVM) is controversial. OBJECTIVE: To analyze in a multicenter, retrospective cohort study, the outcomes following radiosurgery for unruptured AVMs and determine predictive factors. METHODS: We evaluated and pooled AVM radiosurgery data from 8 institutions participating in the International Gamma Knife Research Foundation. Patients with unruptured AVMs and ≥12 mo of follow-up were included in the study cohort. Favorable outcome was defined as AVM obliteration, no postradiosurgical hemorrhage, and no permanently symptomatic radiation-induced changes. RESULTS: The unruptured AVM cohort comprised 938 patients with a median age of 35 yr. The median nidus volume was 2.4 cm 3 , 71% of AVMs were located in eloquent brain areas, and the Spetzler-Martin grade was III or higher in 57%. The median radiosurgical margin dose was 21 Gy and follow-up was 71 mo. AVM obliteration was achieved in 65%. The annual postradiosurgery hemorrhage rate was 1.4%. Symptomatic and permanent radiation-induced changes occurred in 9% and 3%, respectively. Favorable outcome was achieved in 61%. In the multivariate logistic regression analysis, smaller AVM maximum diameter ( P = .001), the absence of AVM-associated arterial aneurysms ( P = .001), and higher margin dose ( P = .002) were found to be independent predictors of a favorable outcome. A margin dose ≥ 20 Gy yielded a significantly higher rate of favorable outcome (70% vs 36%; P < .001). CONCLUSION: Radiosurgery affords an acceptable risk to benefit profile for patients harboring unruptured AVMs. These findings justify further prospective studies comparing radiosurgical intervention to conservative management for unruptured AVMs.

Stereotactic Radiosurgery for ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations)-Eligible Spetzler-Martin Grade I and II Arteriovenous Malformations: A Multicenter Study.

OBJECTIVE: ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations) found better short-term outcomes after conservative management compared with intervention for unruptured arteriovenous malformations (AVMs). However, because Spetzler-Martin (SM) grade I-II AVMs have the lowest treatment morbidity, sufficient follow-up of these lesions may show a long-term benefit from intervention. The aim of this multicenter, retrospective cohort study is to assess the outcomes after stereotactic radiosurgery (SRS) for ARUBA-eligible SM grade I-II AVMs. METHODS: We pooled SRS data for patients with AVM from 7 institutions and selected ARUBA-eligible SM grade I-II AVMs with ≥12 months follow-up for analysis. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes. RESULTS: The ARUBA-eligible SM grade I-II AVM cohort comprised 232 patients (mean age, 42 years). The mean nidus volume, SRS margin dose, and follow-up duration were 2.1 cm3, 22.5 Gy, and 90.5 months, respectively. The actuarial obliteration rates at 5 and 10 years were 72% and 87%, respectively; annual post-SRS hemorrhage rate was 1.0%; symptomatic and permanent radiation-induced changes occurred in 8% and 1%, respectively; and favorable outcome was achieved in 76%. Favorable outcome was significantly more likely in patients treated with a margin dose >20 Gy (83%) versus ≤20 Gy (62%; P < 0.001). Stroke or death occurred in 10% after SRS. CONCLUSIONS: For ARUBA-eligible SM grade I-II AVMs, long-term SRS outcomes compare favorably with the natural history. SRS should be considered for adult patients harboring unruptured, previously untreated low-grade AVMs with a minimum life expectancy of a decade.

Stereotactic radiosurgery for cerebral arteriovenous malformations: evaluation of long-term outcomes in a multicenter cohort.

OBJECTIVE In this multicenter study, the authors reviewed the results following Gamma Knife radiosurgery (GKRS) of cerebral arteriovenous malformations (AVMs), determined predictors of outcome, and assessed predictive value of commonly used grading scales based upon this large cohort with long-term follow-up. METHODS Data from a cohort of 2236 patients undergoing GKRS for cerebral AVMs were compiled from the International Gamma Knife Research Foundation. Favorable outcome was defined as AVM obliteration and no posttreatment hemorrhage or permanent symptomatic radiation-induced complications. Patient and AVM characteristics were assessed to determine predictors of outcome, and commonly used grading scales were assessed. RESULTS The mean maximum AVM diameter was 2.3 cm, with a mean volume of 4.3 cm3. A mean margin dose of 20.5 Gy was delivered. Mean follow-up was 7 years (range 1-20 years). Overall obliteration was 64.7%. Post-GRKS hemorrhage occurred in 165 patients (annual risk 1.1%). Radiation-induced imaging changes occurred in 29.2%; 9.7% were symptomatic, and 2.7% had permanent deficits. Favorable outcome was achieved in 60.3% of patients. Patients with prior nidal embolization (OR 2.1, p < 0.001), prior AVM hemorrhage (OR 1.3, p = 0.007), eloquent location (OR 1.3, p = 0.029), higher volume (OR 1.01, p < 0.001), lower margin dose (OR 0.9, p < 0.001), and more isocenters (OR 1.1, p = 0.011) were more likely to have unfavorable outcomes in multivariate analysis. The Spetzler-Martin grade and radiosurgery-based AVM score predicted outcome, but the Virginia Radiosurgery AVM Scale provided the best assessment. CONCLUSIONS GKRS for cerebral AVMs achieves obliteration and avoids permanent complications in the majority of patients. Patient, AVM, and treatment parameters can be used to predict long-term outcomes following radiosurgery.

Stereotactic radiosurgery for cerebellar arteriovenous malformations: an international multicenter study.

OBJECTIVE Cerebellar arteriovenous malformations (AVMs) represent the majority of infratentorial AVMs and frequently have a hemorrhagic presentation. In this multicenter study, the authors review outcomes of cerebellar AVMs after stereotactic radiosurgery (SRS). METHODS Eight medical centers contributed data from 162 patients with cerebellar AVMs managed with SRS. Of these patients, 65% presented with hemorrhage. The median maximal nidus diameter was 2 cm. Favorable outcome was defined as AVM obliteration and no posttreatment hemorrhage or permanent radiation-induced complications (RICs). Patients were followed clinically and radiographically, with a median follow-up of 60 months (range 7-325 months). RESULTS The overall actuarial rates of obliteration at 3, 5, 7, and 10 years were 38.3%, 74.2%, 81.4%, and 86.1%, respectively, after single-session SRS. Obliteration and a favorable outcome were more likely to be achieved in patients treated with a margin dose greater than 18 Gy (p < 0.001 for both), demonstrating significantly better rates (83.3% and 79%, respectively). The rate of latency preobliteration hemorrhage was 0.85%/year. Symptomatic post-SRS RICs developed in 4.5% of patients (n = 7). Predictors of a favorable outcome were a smaller nidus (p = 0.0001), no pre-SRS embolization (p = 0.003), no prior hemorrhage (p = 0.0001), a higher margin dose (p = 0.0001), and a higher maximal dose (p = 0.009). The Spetzler-Martin grade was not found to be predictive of outcome. The Virginia Radiosurgery AVM Scale score (p = 0.0001) and the Radiosurgery-Based AVM Scale score (p = 0.0001) were predictive of a favorable outcome. CONCLUSIONS SRS results in successful obliteration and a favorable outcome in the majority of patients with cerebellar AVMs. Most patients will require a nidus dose of higher than 18 Gy to achieve these goals. Radiosurgical and not microsurgical scales were predictive of clinical outcome after SRS.

Early versus late arteriovenous malformation responders after stereotactic radiosurgery: an international multicenter study.

OBJECTIVE The goal of stereotactic radiosurgery (SRS) for arteriovenous malformation (AVM) is complete nidus obliteration, thereby eliminating the risk of future hemorrhage. This outcome can be observed within the first 18 months, although documentation of AVM obliteration can extend to as much as 5 years after SRS is performed. A shorter time to obliteration may impact the frequency and effect of post-SRS complications and latency hemorrhage. The authors' goal in the present study was to determine predictors of early obliteration (18 months or less) following SRS for cerebral AVM. METHODS Eight centers participating in the International Gamma Knife Research Foundation (IGKRF) obtained institutional review board approval to supply de-identified patient data. From a cohort of 2231 patients, a total of 1398 patients had confirmed AVM obliteration. Patients were sorted into early responders (198 patients), defined as those with confirmed nidus obliteration at or prior to 18 months after SRS, and late responders (1200 patients), defined as those with confirmed nidus obliteration more than 18 months after SRS. The median clinical follow-up time was 63.7 months (range 7-324.7 months). RESULTS Outcome parameters including latency interval hemorrhage, mortality, and favorable outcome were not significantly different between the 2 groups. Radiologically demonstrated radiation-induced changes were noted more often in the late responder group (376 patients [31.3%] vs 39 patients [19.7%] for early responders, p = 0.005). Multivariate independent predictors of early obliteration included a margin dose > 24 Gy (p = 0.031), prior surgery (p = 0.002), no prior radiotherapy (p = 0.025), smaller AVM nidus (p = 0.002), deep venous drainage (p = 0.039), and nidus location (p < 0.0001). Basal ganglia, cerebellum, and frontal lobe nidus locations favored early obliteration (p = 0.009). The Virginia Radiosurgery AVM Scale (VRAS) score was significantly different between the 2 responder groups (p = 0.039). The VRAS score was also shown to be predictive of early obliteration on univariate analysis (p = 0.009). For early obliteration, such prognostic ability was not shown for other SRS- and AVM-related grading systems. CONCLUSIONS Early obliteration (≤ 18 months post-SRS) was more common in patients whose AVMs were smaller, located in the frontal lobe, basal ganglia, or cerebellum, had deep venous drainage, and had received a margin dose > 24 Gy.

Stereotactic radiosurgery for Spetzler-Martin Grade III arteriovenous malformations: an international multicenter study.

OBJECTIVE Because of the angioarchitectural diversity of Spetzler-Martin (SM) Grade III arteriovenous malformations (AVMs), the management of these lesions is incompletely defined. The aims of this multicenter, retrospective cohort study were to evaluate the outcomes after stereotactic radiosurgery (SRS) for SM Grade III AVMs and to determine the factors predicting these outcomes. METHODS The authors analyzed and pooled data from patients with SM Grade III AVMs treated with SRS at 8 institutions participating in the International Gamma Knife Research Foundation. Patients with these AVMs and a minimum follow-up length of 12 months were included in the study cohort. An optimal outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RICs). Data were analyzed by univariate and multivariate regression analyses. RESULTS The SM Grade III AVM cohort comprised 891 patients with a mean age of 34 years at the time of SRS. The mean nidus volume, radiosurgical margin dose, and follow-up length were 4.5 cm3, 20 Gy, and 89 months, respectively. The actuarial obliteration rates at 5 and 10 years were 63% and 78%, respectively. The annual postradiosurgery hemorrhage rate was 1.2%. Symptomatic and permanent RICs were observed in 11% and 4% of the patients, respectively. Optimal outcome was achieved in 56% of the patients and was significantly more frequent in cases of unruptured AVMs (OR 2.3, p < 0.001). The lack of a previous hemorrhage (p = 0.037), absence of previous AVM embolization (p = 0.002), smaller nidus volume (p = 0.014), absence of AVM-associated arterial aneurysms (p = 0.023), and higher margin dose (p < 0.001) were statistically significant independent predictors of optimal outcome in a multivariate analysis. CONCLUSIONS Stereotactic radiosurgery provided better outcomes for patients with small, unruptured SM Grade III AVMs than for large or ruptured SM Grade III nidi. A prospective trial or registry that facilitates a comparison of SRS with conservative AVM management might further clarify the authors' observations for these often high-risk AVMs.

Stereotactic radiosurgery for intracranial hemangiopericytomas: a multicenter study.

OBJECTIVE Hemangiopericytomas (HPCs) are rare tumors widely recognized for their aggressive clinical behavior, high recurrence rates, and distant and extracranial metastases even after a gross-total resection. The authors report a large multicenter study, through the International Gamma Knife Research Foundation (IGKRF), reviewing management and outcome following stereotactic radiosurgery (SRS) for recurrent or newly discovered HPCs. METHODS Eight centers participating in the IGKRF participated in this study. A total of 90 patients harboring 133 tumors were identified. Patients were included if they had a histologically diagnosed HPC managed with SRS during the period 1988-2014 and had a minimum of 6 months' clinical and radiological follow-up. A de-identified database was created. The patients' median age was 48.5 years (range 13-80 years). Prior treatments included embolization (n = 8), chemotherapy (n = 2), and fractionated radiotherapy (n = 34). The median tumor volume at the time of SRS was 4.9 cm3 (range 0.2-42.4 cm3). WHO Grade II (typical) HPCs formed 78.9% of the cohort (n = 71). The median margin and maximum doses delivered were 15 Gy (range 2.8-24 Gy) and 32 Gy (range 8-51 Gy), respectively. The median clinical and radiographic follow-up periods were 59 months (range 6-190 months) and 59 months (range 6-183 months), respectively. Prognostic variables associated with local tumor control and post-SRS survival were evaluated using Cox univariate and multivariate analysis. Actuarial survival after SRS was analyzed using the Kaplan-Meier method. RESULTS Imaging studies performed at last follow-up demonstrated local tumor control in 55% of tumors and 62.2% of patients. New remote intracranial tumors were found in 27.8% of patients, and 24.4% of patients developed extracranial metastases. Adverse radiation effects were noted in 6.7% of patients. During the study period, 32.2% of the patients (n = 29) died. The actuarial overall survival was 91.5%, 82.1%, 73.9%, 56.7%, and 53.7% at 2, 4, 6, 8, and 10 years, respectively, after initial SRS. Local progression-free survival (PFS) was 81.7%, 66.3%, 54.5%, 37.2%, and 25.5% at 2, 4, 6, 8, and 10 years, respectively, after initial SRS. In our cohort, 32 patients underwent 48 repeat SRS procedures for 76 lesions. Review of these 76 treated tumors showed that 17 presented as an in-field recurrence and 59 were defined as an out-of-field recurrence. Margin dose greater than 16 Gy (p = 0.037) and tumor grade (p = 0.006) were shown to influence PFS. The development of extracranial metastases was shown to influence overall survival (p = 0.029) in terms of PFS; repeat (multiple) SRS showed additional benefit. CONCLUSIONS SRS provides a reasonable rate of local tumor control and a low risk of adverse effects. It also leads to neurological stability or improvement in the majority of patients. Long-term close clinical and imaging follow-up is necessary due to the high probability of local recurrence and distant metastases. Repeat SRS is often effective for treating new or recurrent HPCs.

International multicenter cohort study of pediatric brain arteriovenous malformations. Part 2: Outcomes after stereotactic radiosurgery.

OBJECTIVE Pediatric patients (age < 18 years) harboring brain arteriovenous malformations (AVMs) are burdened with a considerably higher cumulative lifetime risk of hemorrhage than adults. Additionally, the pediatric population was excluded from recent prospective comparisons of intervention versus conservative management for unruptured AVMs. The aims of this multicenter, retrospective cohort study are to analyze the outcomes after stereotactic radiosurgery for unruptured and ruptured pediatric AVMs. METHODS We analyzed and pooled AVM radiosurgery data from 7 participating in the International Gamma Knife Research Foundation. Patients younger than 18 years of age who had at least 12 months of follow-up were included in the study cohort. Favorable outcome was defined as AVM obliteration, no post-radiosurgical hemorrhage, and no permanently symptomatic radiation-induced changes (RIC). The post-radiosurgery outcomes of unruptured versus ruptured pediatric AVMs were compared, and statistical analyses were performed to identify predictive factors. RESULTS The overall pediatric AVM cohort comprised 357 patients with a mean age of 12.6 years (range 2.8-17.9 years). AVMs were previously treated with embolization, resection, and fractionated external beam radiation therapy in 22%, 6%, and 13% of patients, respectively. The mean nidus volume was 3.5 cm3, 77% of AVMs were located in eloquent brain areas, and the Spetzler-Martin grade was III or higher in 59%. The mean radiosurgical margin dose was 21 Gy (range 5-35 Gy), and the mean follow-up was 92 months (range 12-266 months). AVM obliteration was achieved in 63%. During a cumulative latency period of 2748 years, the annual post-radiosurgery hemorrhage rate was 1.4%. Symptomatic and permanent radiation-induced changes occurred in 8% and 3%, respectively. Favorable outcome was achieved in 59%. In the multivariate logistic regression analysis, the absence of prior AVM embolization (p = 0.001) and higher margin dose (p < 0.001) were found to be independent predictors of a favorable outcome. The rates of favorable outcome for patients treated with a margin dose ≥ 22 Gy vs < 22 Gy were 78% (110/141 patients) and 47% (101/216 patients), respectively. A margin dose ≥ 22 Gy yielded a significantly higher probability of a favorable outcome (p < 0.001). The unruptured and ruptured pediatric AVM cohorts included 112 and 245 patients, respectively. Ruptured AVMs had significantly higher rates of obliteration (68% vs 53%, p = 0.005) and favorable outcome (63% vs 51%, p = 0.033), with a trend toward a higher incidence of post-radiosurgery hemorrhage (10% vs 4%, p = 0.07). The annual post-radiosurgery hemorrhage rates were 0.8% for unruptured and 1.6% for ruptured AVMs. CONCLUSIONS Radiosurgery is a reasonable treatment option for pediatric AVMs. Obliteration and favorable outcomes are achieved in the majority of patients. The annual rate of latency period hemorrhage after radiosurgery for both ruptured and unruptured pediatric AVM patients conveys a significant risk until the nidus is obliterated.

International multicenter cohort study of pediatric brain arteriovenous malformations. Part 1: Predictors of hemorrhagic presentation.

OBJECTIVE Brain arteriovenous malformations (AVMs) are the most common cause of spontaneous intracranial hemorrhage in pediatric patients (age < 18 years). Since the cumulative lifetime risk of AVM hemorrhage is considerable in children, an improved understanding of the risk factors influencing hemorrhagic presentation may aid in the management of pediatric AVMs. The aims of this first of a 2-part multicenter, retrospective cohort study are to evaluate the incidence and determine the predictors of hemorrhagic presentation in pediatric AVM patients. METHODS The authors analyzed pooled AVM radiosurgery data from 7 institutions participating in the International Gamma Knife Research Foundation (IGKRF). Patients younger than 18 years at the time of radiosurgery and who had at least 12 months of follow-up were included in the study cohort. Patient and AVM characteristics were compared between unruptured and ruptured pediatric AVMs. RESULTS A total of 357 pediatric patients were eligible for analysis, including 112 patients in the unruptured and 245 patients in the ruptured AVM cohorts (69% incidence of hemorrhagic presentation). The annual hemorrhage rate prior to radiosurgery was 6.3%. Hemorrhagic presentation was significantly more common in deep locations (basal ganglia, thalamus, and brainstem) than in cortical locations (frontal, temporal, parietal, and occipital lobes) (76% vs 62%, p = 0.006). Among the factors found to be significantly associated with hemorrhagic presentation in the multivariate logistic regression analysis, deep venous drainage (OR 3.2, p < 0.001) was the strongest independent predictor, followed by female sex (OR 1.7, p = 0.042) and smaller AVM volume (OR 1.1, p < 0.001). CONCLUSIONS Unruptured and ruptured pediatric AVMs have significantly different patient and nidal features. Pediatric AVM patients who possess 1 or more of these high-risk features may be candidates for relatively more aggressive management strategies.

An Overview of Anterior Skull Base Meningiomas and the Endoscopic Endonasal Approach.

Meningiomas represent 30% of all primary brain tumors. Anterior skull base meningiomas represent 8.8% of all meningiomas. Surgical resection is a main treatment option for tumors that are symptomatic and/or growing. Recurrence is directly related to the extent of resection of the tumor, the dural attachment, and pathologic bone. Endoscopic endonasal approaches represent an important addition to the treatment armamentarium for skull base meningiomas. This article provides an overview of meningiomas, with a focus on those of the anterior skull base and their management.