Stereotactic Radiosurgery for Vestibular Schwannoma With Radiographic Brainstem Compression.

OBJECTIVE: The safety of single-treatment stereotactic radiosurgery (SRS) for vestibular schwannoma (VS) with radiographic evidence of brainstem compression but without motor deficit is controversial. Data on linear accelerator (linac)-based SRS in this setting are scarce. We address this with an outcomes report from an unselected series of patients with VS with radiographic brainstem compression treated with linac SRS. METHODS: We included 139 patients with unilateral VS (any size) with radiographic brainstem compression (all without serious brainstem neurological deficits). The SRS prescription dose was 12.5 Gy (single fraction) using 6MV linac-produced photon beams, delivered with a multiple arc technique. Inclusion criteria required at least 1 year of radiographic follow-up with magnetic resonance imaging. The primary endpoint was freedom from serious brainstem toxicity (≥grade 3 Common Terminology Criteria for Adverse Events v5); the secondary was freedom from enlargement (tumor progression or any requiring intervention). We assessed serious cranial nerve complications, excluding hearing loss, defined as Common Terminology Criteria for Adverse Events v5 grade 3 toxicity. RESULTS: Median magnetic resonance imaging follow-up time was 5 years, and median tumor size was 2.5 cm in greatest axial dimension and 5 ml in volume. The median brainstem D0.03 ml=12.6 Gy and median brainstem V10 Gy=0.4 ml. At 5 years, the actuarial freedom from serious brainstem toxicity was 100%, and freedom from tumor enlargement (requiring surgery and/or due to progression) was 90%. Severe facial nerve damage in patients without tumor enlargement was 0.9%. CONCLUSION: Linac-based SRS, as delivered in our series for VS with radiographic brainstem compression, is safe and effective.

Repeat single-fraction stereotactic radiosurgery for recurrent vestibular schwannoma.

Background: Data are scarce on the efficacy of a second radiosurgery (SRS) treatment of vestibular schwannoma that has progressed following initial treatment with SRS. We sought to report the outcome of our repeat SRS series with long-term imaging follow-up. Materials and methods: We retrospectively analyzed 6 patients who met the following criteria: Repeat SRS at our institution between 1995 and 2018; solitary unilateral tumor; no evidence of neurofibromatosis; and magnetic resonance (MR) planning for both SRS treatments. All treatments were delivered with a linear accelerator-based system using head frame immobilization. The prescribed dose to the periphery of the tumor was 12.5 Gy in all initial and repeat SRS treatments, except for one repeat treatment to 10 Gy. Results: Follow-up with MR scan following the second SRS treatment was a median 8.4 years. The tumor control rate (lack of progression) following the second SRS treatment was 83% (5/6). Actuarial 10-year outcomes following repeat SRS were: tumor control, 80%; absolute survival, 80%; and cause-specific survival, 100%. Of the patients with at least minimal hearing retention before initial SRS, none had ipsilateral hearing preservation after initial radiation treatment. Improvement in any pretreatment cranial nerve deficits was not seen. The only permanent grade ≥ 3 toxicity from repeat SRS was a case of infraorbital nerve deficit. No patient developed a stroke, malignant transformation, induced second tumor, or facial nerve deficit. Conclusion: There was excellent overall survival, tumor control, and low morbidity in our series for recurrent vestibular schwannoma submitted to repeat single-fraction SRS, supporting additional studies of this treatment strategy.

A Distinct DNA Methylation Shift in a Subset of Glioma CpG Island Methylator Phenotypes during Tumor Recurrence.

Glioma diagnosis is based on histomorphology and grading; however, such classification does not have predictive clinical outcome after glioblastomas have developed. To date, no bona fide biomarkers that significantly translate into a survival benefit to glioblastoma patients have been identified. We previously reported that the IDH mutant G-CIMP-high subtype would be a predecessor to the G-CIMP-low subtype. Here, we performed a comprehensive DNA methylation longitudinal analysis of diffuse gliomas from 77 patients (200 tumors) to enlighten the epigenome-based malignant transformation of initially lower-grade gliomas. Intra-subtype heterogeneity among G-CIMP-high primary tumors allowed us to identify predictive biomarkers for assessing the risk of malignant recurrence at early stages of disease. G-CIMP-low recurrence appeared in 9.5% of all gliomas, and these resembled IDH-wild-type primary glioblastoma. G-CIMP-low recurrence can be characterized by distinct epigenetic changes at candidate functional tissue enhancers with AP-1/SOX binding elements, mesenchymal stem cell-like epigenomic phenotype, and genomic instability. Molecular abnormalities of longitudinal G-CIMP offer possibilities to defy glioblastoma progression.

Long-term Outcomes After Radiosurgery for Temporal Bone Paragangliomas.

OBJECTIVES: To determine the long-term outcome after stereotactic radiosurgery (SRS) for temporal bone paragangliomas. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 11 patients with temporal bone paragangliomas (10 patients with a glomus jugulare tumor and 1 patient with a glomus tympanicum tumor) treated between January 1997 and July 2012 at the University of Florida with SRS to a median dose of 15 Gy in 1 fraction. Ten previously unirradiated patients received SRS as did 1 patient who received prior fractionated radiotherapy (FRT) and then received salvage SRS for a local recurrence. The major outcome endpoint was local control, meaning no further growth or shrinkage on follow-up computed tomography or magnetic resonance imaging scans. RESULTS: The median follow-up time was 5.3 years. Two patients developed a local recurrence after SRS, including the patient who received salvage SRS after prior FRT. The overall local control rates at 5 and 10 years were both 81%. The cause-specific survival rates at 5 and 10 years were both 88%. The distant metastasis-free survival rates at 5 and 10 years were both 100%. The overall survival rates at 5 and 10 years were both 78%. There were no severe complications. CONCLUSIONS: SRS for benign head and neck paragangliomas is a safe and efficacious treatment associated with minimal morbidity. SRS is suitable for patients with skull base tumors <3 cm when FRT is logistically unsuitable. Surgery is reserved for patients in good health whose risk of associated morbidity is low. Observation is a reasonable option for asymptomatic patients with a limited life expectancy.

The risk of malignancy anywhere in the body after linear accelerator (LINAC) stereotactic radiosurgery.

BACKGROUND: Despite the conformity of stereotactic radiosurgery (SRS) treatment, there are concerns about the risk of malignancy. OBJECTIVE: We compared the number of cancer cases observed after treatment in a group of SRS patients to the number of cancer cases that would be expected in an age- and gender-matched group. METHODS: We collected data from the University of Florida SRS database for patients treated for meningiomas, intracranial schwannomas, arteriovenous malformations (AVMs), trigeminal neuralgia, pituitary adenomas, cavernous angiomas, and metastases. We used the Florida Cancer Data System (FCDS) to determine the actual cancer rates for SRS-treated patients, and we compared these to the cancer rates in similar groups of non-SRS-treated patients based on rates available from the SEER (surveillance epidemiology and end results) database. RESULTS: A total of 2,369 patients were analyzed. Of these, 862 were patients with metastases who were analyzed only to ensure the sensitivity of using the FCDS to determine malignancy rates. The results for patients with more than 5 years of follow-up are reported. Without the metastases patients, a total of 627 patients had more than 5 years of follow-up data. Follow-up in patient-years was 1,711 for the meningioma patients, 1,851 for the schwannoma patients, 1,407 for the AVM patients and 338 for patients with a diagnosis of 'other'. The observed cancer rate in the meningioma patients was 3.96% compared to the expected rate of 10% (binomial 95% confidence interval, CI = 1.85-7.94). The observed cancer rate in the schwannoma patients was 4.93% compared to the expected rate of 12.5% (95% CI = 2.61-8.89). The observed cancer rate in the AVM patients was 3.64% compared to the expected rate of 4.43% (95% CI = 1.49-8.10). The observed cancer rate in patients treated for other diagnoses (e.g. pituitary adenoma or trigeminal neuralgia) was 0% compared to the expected rate of 6.36% (95% CI = 0-11.7). CONCLUSIONS: In a large population of SRS-treated patients, there was no increased risk of malignancy compared to the general population.

The science of medical decision making: neurosurgery, errors, and personal cognitive strategies for improving quality of care.

During the last 2 decades, there has been a shift in the U.S. health care system towards improving the quality of health care provided by enhancing patient safety and reducing medical errors. Unfortunately, surgical complications, patient harm events, and malpractice claims remain common in the field of neurosurgery. Many of these events are potentially avoidable. There are an increasing number of publications in the medical literature in which authors address cognitive errors in diagnosis and treatment and strategies for reducing such errors, but these are for the most part absent in the neurosurgical literature. The purpose of this article is to highlight the complexities of medical decision making to a neurosurgical audience, with the hope of providing insight into the biases that lead us towards error and strategies to overcome our innate cognitive deficiencies. To accomplish this goal, we review the current literature on medical errors and just culture, explain the dual process theory of cognition, identify common cognitive errors affecting neurosurgeons in practice, review cognitive debiasing strategies, and finally provide simple methods that can be easily assimilated into neurosurgical practice to improve clinical decision making.

Readmissions in neurosurgery: a qualitative inquiry.

OBJECTIVE: To identify deficiencies leading to readmissions to the University of Florida Neurosurgery Service by using the Institute for Healthcare Improvement STate Action on Avoidable Rehospitalizations Readmissions diagnostic tool and to report the opinions of patients, their families, and health care providers. METHODS: A retrospective review of hospital admission and discharge data was conducted. All patients who met eligibility criteria and who were discharged from the neurosurgery service between January 1 and March 31, 2012, and readmitted within 30 days after discharge (n=74; 66 patients; 7 multiple readmissions) were included. A chart review revealed potential precipitating factors. Health care providers, patients, and family members were also interviewed. Median values and frequencies were used to summarize the data. RESULTS: The 30-day readmission rate on the neurosurgery service was 14%. Problems associated with wound care accounted for 24% of readmissions, neurologic conditions accounted for 50%, and other medical conditions accounted for 26%. Patients and providers agreed on the medical diagnoses resulting in readmission, but providers also often named "patient noncompliance" as a factor leading to readmission, whereas patients often thought they either were "sent home too early" or had a "general decline with no improvement." CONCLUSIONS: Systematic patterns and common themes associated with patient readmissions were identified for a neurosurgical service. These findings are now being used to implement changes in discharge planning.

Intracranial arteriovenous malformation in a college football player and return-to-play considerations.

: The reported prevalence rates of arteriovenous malformations (AVMs) in the general population range from 0.001% to 0.50%. The following case describes the initial presentation of hemorrhage from an intracranial AVM in an 18-year-old college football player. It also discusses treatment of the AVM with stereotactic radiosurgery and successful return to football 17 months after radiosurgery (18.5 months after initial presentation). It is the first published description of return to contact sports after stereotactic radiosurgery for intracranial AVM.

Follow-up on a national survey: american neurosurgery resident opinions on the 2011 accreditation council for graduate medical education-implemented duty hours.

OBJECTIVE: We previously performed a nationwide survey of American neurosurgical residents before the initiation of the 2011 Accreditation Council for Graduate Medical Education regulations, in which more than 70% indicated the proposed changes would negatively impact residency training. We sought to resurvey the resident population as to the actual changes that occurred to their programs after the 2011 standards went into effect. METHODS: Surveys were mailed to every neurosurgery training program in the United States and Puerto Rico. Program directors and coordinators were asked to distribute surveys to their residents. RESULTS: A total of 253 neurosurgery residents responded. Reported duty-hour violations were largely unchanged after the 2011 duty-hour changes. Sixty-percent of residents reported that they had underreported duty hours, with nearly 25% of respondents doing so on a weekly or daily basis. Most reported that the 2011 changes had not affected operative caseload, academic productivity, quality of life, or resident fatigue. The majority of residents disagreed or strongly disagreed that the PGY-1 16-hour limitation had a positive impact on first-year resident training (69%) or had improved patient safety (62%). Overall, the majority of respondents reported that the 2011 changes had a negative (35%) or negligible (33%) effect on residency training at their institution. CONCLUSION: Respondents indicated that the 2011 Accreditation Council for Graduate Medical Education regulations have had a smaller perceived effect on neurosurgical training programs than previously predicted. However, the majority of residents admitted to underreporting duty hours, with a quarter doing so on a regular basis. The 16-hour rule for interns remains unpopular.

Stereotactic radiosurgery of intracranial arteriovenous malformations.

Stereotactic radiosurgery for intracranial arteriovenous malformations (AVMs) has been performed since the 1970s. When an AVM is treated with radiosurgery, radiation injury to the vascular endothelium induces the proliferation of smooth muscle cells and the elaboration of extracellular collagen, which leads to progressive stenosis and obliteration of the AVM nidus. Obliteration after AVM radiosurgery ranges from 60% to 80%, and relates to the size of the AVM and the prescribed radiation dose. The major drawback of radiosurgical AVM treatment is the risk of bleeding during the latent period (typically 2 years) between treatment and AVM thrombosis.

Mixed-reality simulation for neurosurgical procedures.

BACKGROUND: Surgical education is moving rapidly to the use of simulation for technical training of residents and maintenance or upgrading of surgical skills in clinical practice. To optimize the learning exercise, it is essential that both visual and haptic cues are presented to best present a real-world experience. Many systems attempt to achieve this goal through a total virtual interface. OBJECTIVE: To demonstrate that the most critical aspect in optimizing a simulation experience is to provide the visual and haptic cues, allowing the training to fully mimic the real-world environment. METHODS: Our approach has been to create a mixed-reality system consisting of a physical and a virtual component. A physical model of the head or spine is created with a 3-dimensional printer using deidentified patient data. The model is linked to a virtual radiographic system or an image guidance platform. A variety of surgical challenges can be presented in which the trainee must use the same anatomic and radiographic references required during actual surgical procedures. RESULTS: Using the aforementioned techniques, we have created simulators for ventriculostomy, percutaneous stereotactic lesion procedure for trigeminal neuralgia, and spinal instrumentation. The design and implementation of these platforms are presented. CONCLUSION: The system has provided the residents an opportunity to understand and appreciate the complex 3-dimensional anatomy of the 3 neurosurgical procedures simulated. The systems have also provided an opportunity to break procedures down into critical segments, allowing the user to concentrate on specific areas of deficiency.

Magnetic resonance imaging assessment of cerebral arteriovenous malformation obliteration after stereotactic radiosurgery.

BACKGROUND: Stereotactic radiosurgery is ideal for treating small cerebral arteriovenous malformations (AVMs) that are surgically inaccessible. However, given the inherent delay of AVM obliteration and the potential for radiosurgical failure, detailed evaluation of the neurovascular architecture is necessary to monitor persistence of residual flow. Modern imaging systems such as magnetic resonance imaging (MRI) and angiography allow clinicians to assess transnidus flow after radiosurgical intervention. OBJECTIVE: To determine the accuracy of an MRI diagnosis of complete thrombosis and to identify variables that affect the precision of MRI assessment. METHODS: One hundred twenty patients were reviewed after receiving radiosurgery at the University of Florida from 1990 to 2010. Each patient had an MRI demonstrating AVM obliteration and an angiogram either confirming or denying AVM thrombosis. RESULTS: MRI correctly predicted complete AVM obliteration in 82% of patients. There was a significant correlation between AVM volume and MRI accuracy in 2 separate models. In the first model, logistic regression analysis revealed a significant linear relationship between the natural log of AVM volume and MRI accuracy. The second model showed significant evidence of a cutoff point in MRI accuracy near an AVM volume of 2.80 cm(3), above which MRI agreement with angiography is 90% and below which MRI agreement falls off sharply to remain constant at 70%. CONCLUSION: MRI is a useful diagnostic system for assessing AVM obliteration, but its accuracy is inherently linked to the nidus volume it is measuring. These results suggest that MRI may be able to take on an increasingly independent role in the evaluation of AVM regression.

Decreasing ventricular infections through the use of a ventriculostomy placement bundle: experience at a single institution.

OBJECT: Ventricular infection after ventriculostomy placement carries a high mortality rate. Responding to ventriculostomy infection rates, a multidisciplinary performance improvement team was formed, a comprehensive protocol for ventriculostomy placement was developed, and the efficacy was evaluated. METHODS: A best-practice protocol was developed, including hand hygiene before the procedure; prophylactic antibiotics; sterile gloves changed between preparation, draping, and procedure; hair removal by clipping for dressing adherence; skin preparation using iodine povacrylex (0.7% available iodine) and isopropyl alcohol (74%); full body and head drape; full surgical attire for the surgeon and other bedside providers; and an antimicrobial-impregnated catheter. A checklist of critical components was used to confirm proper insertion and to monitor practice. Procedure-specific infection rates were calculated using the number of infections divided by the number of patients in whom an external ventricular drainage (EVD) device was inserted × 100 (%). Data were reported back to providers and to the committee. Bundle compliance was monitored over a 4-year period. RESULTS: At the authors' institution, 2928 ventriculostomies were performed between the beginning of the fourth quarter of 2006 and the end of the first quarter of 2012. Although the best-evidence bundle was applied to all patients, only 588 (20.1%) were checklist monitored (increasing from 7% to 23% over the study period). The infection rate for the 2 quarters before bundle implementation was 9.2%. During the study period, the rate decreased quarterly to 2.6% and then to 0%. Over a 4-year period, the rate was 1.06% (2007), 0.66% (2008), 0.15% (2009), and 0.34% (2010); it was 0% in 2011 and the first quarter of 2012. The overall EVD infection rate was 0.46% after bundle implementation. CONCLUSIONS: Bundle implementation including an antimicrobial-impregnated catheter dramatically decreased EVD-related infections. Training and situational awareness of appropriate practice, assisted by the checklist, plus use of the antibiotic-impregnated catheter resulted in sustained reduction in ventriculitis.

Reducing ventriculostomy-related infections to near zero: the eliminating ventriculostomy infection study.

Implementation of a standard protocol and use of antibiotic-coated ventricular catheters helped reduce EVD-related infections from 9.2% to almost zero at the University of Florida. This project demonstrated the success of creating a task force to identify areas of improvement, implement solutions, and monitor the outcomes.

Radiographic response of brain metastasis after linear accelerator radiosurgery.

BACKGROUND: Radiographic response of brain metastasis to stereotactic radiosurgery (SRS) over time has not been well characterized. Being able to predict SRS-induced changes in tumor size over time may allow improved counseling of patients and potentially earlier recognition of poor response to SRS. OBJECTIVE: To quantify the rate of change in size of metastatic brain tumors after treatment with a linear accelerator (LINAC) SRS. METHODS: We performed a retrospective analysis of patients with single metastatic brain tumors treated with LINAC SRS at the University of Florida between 1992 and 2009 who had at least one MRI after treatment. A total of 218 patients with 406 follow-up MRI scans were included in the study. Tumor area was calculated by measuring the largest tumor area on axial imaging and using the equation for area of an ellipse. Primary outcome was percent change in tumor size. The contribution of several factors including gender, primary tumor histology, synchronous or asynchronous presentation, prior treatment, primary tumor control, and SRS dose were examined using multivariate analysis. RESULTS: Mean patient age was 58.3 years (range 4-86), and 48.6% of patients were female. Sixty-three percent of patients had primary tumor control and 70.6% had asynchronous presentation of their brain metastases. SRS peripheral dose range was 1,000-2,250 cGy with a median of 1,750 cGy. The mean percent size change was -22.6% with a mean rate of change of -7.0% per month. The median percent change was -49.7% with a median rate of change of -8.8% per month. The median follow-up was 4.8 months (range 0.3-52.5). Female gender and melanoma histology were found to be significant predictors of an increase in tumor size. Lack of previous surgical resection was a significant predictor of a decrease in tumor size after SRS. Other factors tested with multivariate analysis, including age, synchronicity of presentation, dose, dose volume, Karnofsky performance score, and primary tumor control, were not significant in predicting tumor size change after SRS. CONCLUSION: In this study, brain metastases decreased in size by a median of 50% for a median follow-up of 4.8 months after SRS. The overall rate of decrease was 9% per month after treatment with SRS. Melanoma histology was a predictor of poor tumor control.

Repeat radiosurgery for intracranial arteriovenous malformations.

BACKGROUND: Despite a high success rate in the stereotactic radiosurgical treatment of intracranial arteriovenous malformations (AVMs) that cannot be safely resected with microsurgery, some patients must be managed after treatment failure. OBJECTIVE: To provide an update on the use of repeat linear accelerator radiosurgery as a treatment for failed AVM radiosurgery at the University of Florida. METHODS: We reviewed 103 patients who underwent repeat radiosurgical treatment for residual AVM at the University of Florida between December 1991 and December 2007. Each of these patients had at least 2 radiosurgical treatments for the same AVM. Patient information, including AVM nidus volume, prescription dose, age, and sex, was collected at the time of initial treatment and again at the time of retreatment. Patients were followed up after treatment with magnetic resonance, computed tomography, and angiographic imaging at standard intervals to determine the status of their AVM. The median follow-up after retreatment was 31 months. RESULTS: Between the first and second treatments, the median AVM nidus volume was decreased by 69% (from a median volume of 12.7 to 4.0 cm), allowing the median prescribed dose to be increased from 1500 cGy on initial treatment to 1750 cGy on retreatment. The final obliteration rate on retreatment was 65.3%. After salvage retreatment, 5 patients (4.9%) experienced radiation-induced complications, and 6 patients (5.8%) experienced posttreatment hemorrhage. CONCLUSION: Repeat radiosurgery is a safe and effective salvage treatment for AVMs.