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Objective: The goal of this study was to characterize local tumor control (LC), overall survival (OS), and safety of stereotactic radiosurgery for colorectal brain metastasis (CRBM)., Methods: Ten international institutions participating in the International Radiosurgery Research Foundation provided data for this retrospective case series. This study included 187 patients with CRBM (281 tumors), with a median age of 62 years and 56.7% being male. Most patients (53.5%) had solitary tumors, although 10.7% had > 5 tumors. The median tumor volume was 2.7 cm3 (IQR 0.22-8.1 cm3), and the median margin dose was 20 Gy (IQR 18-22 Gy)., Results: The 3-year LC and OS rates were 72% and 20%, respectively. Symptomatic adverse radiation effects occurred in 1.6% of patients. In the multivariate analysis, age > 65 years and tumor volume > 4.0 cm3 were significant predictors of tumor progression (hazard ratio [HR] 2.6, 95% CI 1.4-4.9; p = 0.003 and HR 3.4, 95% CI 1.7-6.9; p < 0.001, respectively). Better performance status (Karnofsky Performance Scale score > 80) was associated with a reduced risk of tumor progression (HR 0.38, 95% CI 0.19-0.73; p = 0.004). Patient age > 62 years (HR 1.6, 95% CI 1.1-2.3; p = 0.03) and the presence of active extracranial disease (HR 1.7, 95% CI 1.1-2.4; p = 0.009) were significantly associated with worse OS., Conclusions: Stereotactic radiosurgery offers a high LC rate and a low rate of symptomatic adverse radiation effects for the majority of CRBMs. The OS and LC favored younger patients with high functional performance scores and inactive extracranial disease.

Background: There are limited data regarding outcomes for patients with gastrointestinal (GI) primaries and brain metastases treated with stereotactic radiosurgery (SRS)., Objective: To examine clinical outcomes after SRS for patients with brain metastases from GI primaries and evaluate potential prognostic factors., Methods: The International Radiosurgery Research Foundation centers were queried for patients with brain metastases from GI primaries managed with SRS. Primary outcomes were local control (LC) and overall survival (OS). Kaplan-Meier analysis was used for univariate analysis (UVA) of prognostic factors. Factors significant on UVA were evaluated with a Cox multivariate analysis proportional hazards model. Logistic regressions were used to examine correlations with RN., Results: We identified 263 eligible patients with 543 brain metastases. Common primary sites were rectal (31.2%), colon (31.2%), and esophagus (25.5%) with a median age of 61.6 years (range: 37-91.4 years) and a median Karnofsky performance status (KPS) of 90% (range: 40%-100%). One-year and 2-year LC rates were 83.5% (95% CI: 78.9%-87.1%) and 73.0% (95% CI: 66.4%-78.5%), respectively. On UVA, age >65 years ( P = .001), dose <20 Gy ( P = .006) for single-fraction plans, KPS <90% ( P < .001), and planning target volume ≥2cc ( P = .007) were associated with inferior LC. All factors other than dose were significant on multivariate analysis ( P ≤ .002). One-year and 2-year OS rates were 68.0% (95% CI: 61.5%-73.6%) and 31.2% (95% CI: 24.6%-37.9%), respectively. Age > 65 years ( P = .006), KPS <90% ( P = .005), and extracranial metastases ( P = .05) were associated with inferior OS., Conclusion: SRS resulted in comparable LC with common primaries. Age and KPS were associated with both LC and OS with planning target volume and extracranial metastases correlating with LC and OS, respectively. These factors should be considered in GI cancer patient selection for SRS., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Purpose: Service development to improve patient safety and experience, and improve staff safety and confidence when managing telephone calls from parents or carers of children with cancer in the UK., Method: A multi-layered mixed methods approach broadly based on sequential PDSA (plan, do, study, act) cycles, to a series of quality initiative projects spanning 14 years. Various project styles and methods are described., Results: A Telephone Triage Toolkit for children's cancer services was piloted, reviewed and rolled out across the UK. Similarities were identified between adult and paediatric cancer services when identifying the case for need, enabling partnership working. A scheduled review completed in 2020 included new developments in cancer treatment, building on user experience, local audits and national feedback, leading to a 2nd edition being implemented., Conclusions: Ground up, quality initiatives and collaborative working across organisations can be complex but draws on a wider pool of expertise and can lead to improved parent and staff experience of services. This initiative has improved practice and has application outside the UK., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: The optimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. One approach is volume-staged stereotactic radiosurgery (VS-SRS). The authors previously reported efficacy of VS-SRS for large AVMs in a multiinstitutional cohort; here they focus on risk of symptomatic adverse radiation effects (AREs)., Methods: This is a multicentered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM, with volume stages separated by intervals of 3-6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. The authors evaluated permanent, transient, and total ARE events that were symptomatic., Results: Patients received 2-4 total volume stages. The median age was 33 years at the time of the first SRS volume stage, and the median follow-up was 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cm3 (range 7.7-94.4 cm3), with a median margin dose per stage of 17 Gy (range 12-20 Gy). A total of 64 patients (25%) experienced an ARE, of which 19 were permanent. Rather than volume, maximal linear dimension in the Z (craniocaudal) dimension was associated with toxicity; a threshold length of 3.28 cm was associated with an ARE, with a 72.5% sensitivity and a 58.3% specificity. In addition, parietal lobe involvement for superficial lesions and temporal lobe involvement for deep lesions were associated with an ARE., Conclusions: Size remains the dominant predictor of toxicity following SRS, but overall rates of AREs were lower than anticipated based on baseline features, suggesting that dose and size were relatively dissociated through volume staging. Further techniques need to be assessed to optimize outcomes.

Purpose: Proximal Junctional Kyphosis (PJK) is a well-documented phenomenon following spinal instrumented fusion. Myelopathy associated with proximal junctional failure (PJF) is poorly described in the literature. Adjacent segment disease, fracture above the upper instrumented vertebrae and subluxation may all cause cord compression, ambulatory dysfunction, and/or lower extremity weakness in the postoperative period. Materials and methods: We review the literature on PJK and PJF, and discusses the postoperative management of three patients who experienced myelopathy associated with PJF following T9/10 to pelvis fusion at a single institution. Results and conclusions: PJF with myelopathy must be diagnosed and surgically corrected early on so as to minimize permanent neurologic injury. Patients requiring significant sagittal deformity correction are at greater risk for PJF, and may benefit from constructs terminating in the upper thoracic spine.

Objective: Endoscopic-microvascular decompression (E-MVD) is a well-described treatment for trigeminal neuralgia (TGN), but there has been debate on the safety of intraoperative sacrifice of the petrosal vein (PV) due to concern for subsequent venous insufficiency. Our objective was to investigate the risk of PV sacrifice during E-MVD in TGN and subsequent postoperative complications and pain outcomes., Methods: 5 five-year review yielded 201 patients who underwent MVD for TGN. PV sacrifice, vascular compressive anatomy, and postoperative complications attributable to venous insufficiency were analyzed. Preoperative and postoperative pain outcomes were analyzed., Results: PV was sacrificed in 118 of 201 (59%) of patients, with 43 of 201 (21%) patients undergoing partial sacrifice versus 75 of 201 (37%) with complete sacrifice. No cases of venous infarction, cerebellar swelling, or fatal complications were noted in either cohort. Non-neurologic complications occurred in 1.69% (2 of 118) of patients with PV sacrifice and 0% (0 of 83) of patients with PV preservation. Neurologic deficits (facial palsy, conductive hearing loss, gait instability, memory deficit) occurred in equal proportions in PV preservation and sacrifice groups (2.41% vs. 1.69%) Overall, 87.3% (145 of 166) patients reported their pain as "very much improved" or "much improved" at 1 month, and no difference between groups was identified., Conclusions: This study did not find higher complication rates in patients undergoing petrosal vein sacrifice during E-MVD for trigeminal neuralgia. In this series where petrosal vein was sacrificed only 59% of the time, it appears to be a safe technique, but larger studies will be needed to determine true incidence of complications after PV sacrifice., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Optimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. Volume-staged stereotactic radiosurgery (VS-SRS) provides an effective option for these high-risk lesions, but optimizing treatment for these recalcitrant and rare lesions has proven difficult., Methods: This is a multi-centered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM with volume stages separated by intervals of 3-6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. We evaluated near complete response (nCR), obliteration, cure, and overall survival., Results: With a median age of 33 years old at the time of first SRS volume stage, patients received 2-4 total volume stages and a median follow up of 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cc (range: 7.7-94.4 cc) with a median margin dose per stage of 17 Gy (range: 12-20 Gy). Total AVM volume, margin dose per stage, compact nidus, lack of prior embolization, and lack of thalamic location involvement were all associated with improved outcomes. Dose >/= 17.5 Gy was strongly associated with improved rates of nCR, obliteration, and cure. With dose >/= 17.5 Gy, 5- and 10-year cure rates were 33.7% and 76.8% in evaluable patients compared to 23.7% and 34.7% of patients with 17 Gy and 6.4% and 20.6% with <17 Gy per volume-stage (p = 0.004). Obliteration rates in diffuse nidus architecture with <17 Gy were particularly poor with none achieving obliteration compared to 32.3% with doses >/= 17 Gy at 5 years (p = 0.007). Comparatively, lesions with a compact nidus architecture exhibited obliteration rates at 5 years were 10.7% vs 9.3% vs 26.6% for dose >17 Gy vs 17 Gy vs >/=17.5 Gy., Conclusion: VS-SRS is an option for upfront treatment of large AVMs. Higher dose was associated with improved rates of nCR, obliteration, and cure suggesting that larger volumetric responses may facilitate salvage therapy and optimize the chance for cure., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Multidisciplinary treatment including medical oncology, radiation oncology, and surgical consultation is necessary to provide comprehensive therapy for patients with spinal metastases. The goal of this study was to review the use of radiation therapy and/or surgical intervention and their impact on patient outcomes., Methods: In this retrospective series, the authors identified at their institution those patients with spinal metastases who had received radiation therapy alone or had undergone surgery with or without radiation therapy within a 6-year period. Data on patient age, chemotherapy, surgical procedure, radiation therapy, Karnofsky Performance Status (KPS), primary tumor pathology, Spinal Instability Neoplastic Score (SINS), and survival after treatment were collected from the patient electronic medical records. N - 1 chi-square testing was used for comparisons of proportions. The Student t-test was used for comparisons of means. A p value < 0.05 was considered statistically significant. A survival analysis was completed using a multivariate Cox proportional hazards model., Results: Two hundred thirty patients with spinal metastases were identified, 109 of whom had undergone surgery with or without radiation therapy. Among the 104 patients for whom the surgical details were reviewed, 34 (33%) had a history of preoperative radiation to the surgical site but ultimately required surgical intervention. In this surgical group, a significantly increased frequency of death within 30 days was noted for the SINS unstable patients (23.5%) as compared to that for the SINS stable patients (2.3%; p < 0.001). The SINS was a significant predictor of time to death among surgical patients (HR 1.11, p = 0.037). Preoperative KPS was not independently associated with decreased survival (p > 0.5) on univariate analysis. One hundred twenty-six patients met the criteria for inclusion in the radiation-only analysis. Ninety-eight of these patients (78%) met the criteria for potential instability (PI) at the time of treatment, according to the SINS system. Five patients (5%) with PI in the radiation therapy group had a documented neurosurgical or orthopedic surgery consultation prior to radiation therapy., Conclusions: At the authors' institution, patients with gross mechanical instability per the SINS system had an increased rate of 30-day postoperative mortality, which remained significant when controlling for other factors. Surgical consultation for metastatic spine patients receiving radiation oncology consultation with PI is low. The authors describe an institutional pathway to encourage multidisciplinary treatment from the initial encounter in the emergency department to expedite surgical evaluation and collaboration.

Objective: In this multicenter study, the authors reviewed the results obtained in patients who underwent Gamma Knife radiosurgery (GKRS) for dural arteriovenous fistulas (dAVFs) and determined predictors of outcome., Methods: Data from a cohort of 114 patients who underwent GKRS for cerebral dAVFs were compiled from the International Gamma Knife Research Foundation. Favorable outcome was defined as dAVF obliteration and no posttreatment hemorrhage or permanent symptomatic radiation-induced complications. Patient and dAVF characteristics were assessed to determine predictors of outcome in a multivariate logistic regression analysis; dAVF-free obliteration was calculated in a competing-risk survival analysis; and Youden indices were used to determine optimal radiosurgical dose., Results: A mean margin dose of 21.8 Gy was delivered. The mean follow-up duration was 4 years (range 0.5-18 years). The overall obliteration rate was 68.4%. The postradiosurgery actuarial rates of obliteration at 3, 5, 7, and 10 years were 41.3%, 61.1%, 70.1%, and 82.0%, respectively. Post-GRKS hemorrhage occurred in 4 patients (annual risk of 0.9%). Radiation-induced imaging changes occurred in 10.4% of patients; 5.2% were symptomatic, and 3.5% had permanent deficits. Favorable outcome was achieved in 63.2% of patients. Patients with middle fossa and tentorial dAVFs (OR 2.4, p = 0.048) and those receiving a margin dose greater than 23 Gy (OR 2.6, p = 0.030) were less likely to achieve a favorable outcome. Commonly used grading scales (e.g., Borden and Cognard) were not predictive of outcome. Female sex (OR 1.7, p = 0.03), absent venous ectasia (OR 3.4, p < 0.001), and cavernous carotid location (OR 2.1, p = 0.019) were predictors of GKRS-induced dAVF obliteration., Conclusions: GKRS for cerebral dAVFs achieved obliteration and avoided permanent complications in the majority of patients. Those with cavernous carotid location and no venous ectasia were more likely to have fistula obliteration following radiosurgery. Commonly used grading scales were not reliable predictors of outcome following radiosurgery.

Background: Freehand bedside ventriculostomy placement can result in catheter malfunction requiring a revision procedure and cause significant patient morbidity. We performed a single-center retrospective review to assess factors related to this complication., Methods: Using an administrative database and chart review, we identified 101 first-time external ventricular drain placements performed at the bedside. We collected data regarding demographics, medical comorbidities, complications, and catheter tip location. We performed univariate and multivariate statistical analyses using MATLAB. We corrected for multiple comparisons using the false discovery rate (FDR) procedure., Results: Multivariate regression analyses revealed that revision procedures were more likely to occur after drain blockage (odds ratio [OR] 17.9) and hemorrhage (OR 10.3, FDR-corrected P values < 0.01, 0.05, respectively). Drain blockage was less frequent after placement in an "optimal location" (ipsilateral ventricle or near foramen of Monroe; OR 0.09, P = 0.009, FDR-corrected P < 0.03) but was more likely to occur after placement in third ventricle (post-hoc P values < 0.015). Primary diagnoses included subarachnoid hemorrhage (n = 30, 29.7%), intraparenchymal hemorrhage with intraventricular extravasation (n = 24, 23.7%), tumor (n = 20, 19.8%), and trauma (n = 17, 16.8%). Most common complications included drain blockage (n = 12, 11.8%) and hemorrhage (n = 8, 7.9%). In total, 16 patients underwent at least 1 revision procedure (15.8%)., Conclusions: Bedside external ventricular drain placement is associated with a 15% rate of revision, that typically occurred after drain blockage and postprocedure hemorrhage. Optimal placement within the ipsilateral frontal horn or foramen of Monroe was associated with a reduced rate of drain blockage., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Stereotactic radiosurgery (SRS) is a treatment option for persistent or recurrent acromegaly secondary to a growth hormone secreting pituitary adenoma, but its efficacy is inadequately defined., Objective: To assess, in a multicenter, retrospective cohort study, the outcomes of SRS for acromegaly and determine predictors., Methods: We pooled and analyzed data from 10 participating institutions of the International Gamma Knife Research Foundation for patients with acromegaly who underwent SRS with endocrine follow-up of ≥6 mo., Results: The study cohort comprised 371 patients with a mean endocrine follow-up of 79 mo. IGF-1 lowering medications were held in 56% of patients who were on pre-SRS medical therapy. The mean SRS treatment volume and margin dose were 3.0 cm3 and 24.2 Gy, respectively. The actuarial rates of initial and durable endocrine remission at 10 yr were 69% and 59%, respectively. The mean time to durable remission after SRS was 38 mo. Biochemical relapse after initial remission occurred in 9%, with a mean time to recurrence of 17 mo. Cessation of IGF-1 lowering medication prior to SRS was the only independent predictor of durable remission (P = .01). Adverse radiation effects included the development of ≥1 new endocrinopathy in 26% and ≥1 cranial neuropathy in 4%., Conclusion: SRS is a definitive treatment option for patients with persistent or recurrent acromegaly after surgical resection. There appears to be a statistical association between the cessation of IGF-1 lowering medications prior to SRS and durable remission., (Copyright © 2018 by the Congress of Neurological Surgeons.)

OBJECTIVE Meningiomas are the most common benign extramedullary lesions of the foramen magnum; however, their optimal management remains undefined. Given their location, foramen magnum meningiomas (FMMs) can cause significant morbidity, and complete microsurgical removal can be challenging. Anterior and anterolateral FMMs carry greater risks with surgery, but they comprise the majority of these lesions. As an alternative to resection, stereotactic radiosurgery (SRS) has been used to treat FMMs in small case series. To more clearly define the outcomes of SRS and to delineate a rational management paradigm for these lesions, the authors analyzed the safety and efficacy of SRS for FMM in an international multicenter trial. METHODS Seven medical centers participating in the International Gamma Knife Research Foundation (IGKRF) provided data for this retrospective cohort study. Patients who were treated with Gamma Knife radiosurgery and whose clinical and radiological follow-up was longer than 6 months were eligible for study inclusion. Data from pre- and post-SRS radiological and clinical evaluations were analyzed. Stereotactic radiosurgery treatment variables were recorded. RESULTS Fifty-seven patients (39 females and 18 males, with a median age of 64 years) met the study inclusion criteria. Thirty-two percent had undergone prior microsurgical resection. Patients most frequently presented with cranial neuropathy (39%), headache (35%), numbness (32%), and ataxia (30%). Median pre-SRS tumor volume was 2.9 cm 3 . Median SRS margin dose was 12.5 Gy (range 10-16 Gy). At the last follow-up after SRS, 49% of tumors were stable, 44% had regressed, and 7% had progressed. Progression-free survival rates at 5 and 10 years were each 92%. A greater margin dose was associated with a significantly increased likelihood of tumor regression, with 53% of tumors treated with > 12 Gy regressing. Fifty-two percent of symptomatic patients noted some clinical improvement. Adverse radiation effects were limited to hearing loss and numbness in 1 patient (2%). CONCLUSIONS Stereotactic radiosurgery for FMM frequently results in tumor control or tumor regression, as well as symptom improvement. Margin doses > 12 Gy were associated with increased rates of tumor regression. Stereotactic radiosurgery was generally safe and well tolerated. Given its risk-benefit profile, SRS may be particularly useful in the management of small- to moderate-volume anterior and anterolateral FMMs.

Context: Cushing disease (CD) due to adrenocorticotropic hormone-secreting pituitary tumors can be a management challenge., Objective: To better understand the outcomes of stereotactic radiosurgery (SRS) for CD and define its role in management., Design: International, multicenter, retrospective cohort analysis., Setting: Ten medical centers participating in the International Gamma Knife Research Foundation., Patients: Patients with CD with >6 months endocrine follow-up., Intervention: SRS using Gamma Knife radiosurgery., Main Outcome Measures: The primary outcome was control of hypercortisolism (defined as normalization of free urinary cortisol). Radiologic response and adverse radiation effects (AREs) were recorded., Results: In total, 278 patients met inclusion criteria, with a mean follow-up of 5.6 years (0.5 to 20.5 years). Twenty-two patients received SRS as a primary treatment of CD. Mean margin dose was 23.7 Gy. Cumulative initial control of hypercortisolism was 80% at 10 years. Mean time to cortisol normalization was 14.5 months. Recurrences occurred in 18% with initial cortisol normalization. Overall, the rate of durable control of hypercortisolism was 64% at 10 years and 68% among patients who received SRS as a primary treatment. AREs included hypopituitarism (25%) and cranial neuropathy (3%). Visual deficits were related to treatment of tumor within the suprasellar cistern (P = 0.01), whereas both visual (P < 0.0001) and nonvisual cranial neuropathy (P = 0.02) were related to prior pituitary irradiation., Conclusions: SRS for CD is well tolerated and frequently results in control of hypercortisolism. However, recurrences can occur. SRS should be considered for patients with persistent hypercortisolism after pituitary surgery and as a primary treatment in those unfit for surgery. Long-term endocrine follow-up is essential after SRS., (Copyright © 2017 Endocrine Society)

Sleep is an evolutionarily conserved process that is linked to diurnal cycles and normal daytime wakefulness. Healthy sleep and wakefulness are integral to a healthy lifestyle; this occurs when an organism is able to maintain long bouts of both sleep and wake. Homer proteins, which function as adaptors for group 1 metabotropic glutamate receptors, have been implicated in genetic studies of sleep in both Drosophila and mouse. Drosophila express a single Homer gene product that is upregulated during sleep. By contrast, vertebrates express Homer as both constitutive and immediate early gene (H1a) forms, and H1a is up-regulated during wakefulness. Genetic deletion of Homer in Drosophila results in fragmented sleep and in failure to sustain long bouts of sleep, even under increased sleep drive. However, deletion of Homer1a in mouse results in failure to sustain long bouts of wakefulness. Further evidence for the role of Homer1a in the maintenance of wake comes from the CREB alpha delta mutant mouse, which displays a reduced wake phenotype similar to the Homer1a knockout and fails to up-regulate Homer1a upon sleep loss. Homer1a is a gene whose expression is induced by CREB. Sustained behaviors of the sleep/wake cycle are created by molecular pathways that are distinct from those for arousal or short bouts, and implicate an evolutionarily-conserved role for Homer in sustaining these behaviors.