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Jason P Sheehan,
Robert M Starke,
David Mathieu,
Byron Young,
Penny K Sneed,
Veronica L Chiang,
John Y K Lee,
Hideyuki Kano,
Kyung-Jae Park,
Ajay Niranjan,
Douglas Kondziolka,
Gene H Barnett,
Stephen Rush,
John G Golfinos,
L Dade Lunsford
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ABSTRACT: Object Pituitary adenomas are fairly common intracranial neoplasms, and nonfunctioning ones constitute a large subgroup of these adenomas. Complete resection is often difficult and may pose undue risk to neurological and endocrine function. Stereotactic radiosurgery has come to play an important role in the management of patients with nonfunctioning pituitary adenomas. This study examines the outcomes after radiosurgery in a large, multicenter patient population. Methods Under the auspices of the North American Gamma Knife Consortium, 9 Gamma Knife surgery (GKS) centers retrospectively combined their outcome data obtained in 512 patients with nonfunctional pituitary adenomas. Prior resection was performed in 479 patients (93.6%) and prior fractionated external-beam radiotherapy was performed in 34 patients (6.6%). The median age at the time of radiosurgery was 53 years. Fifty-eight percent of patients had some degree of hypopituitarism prior to radiosurgery. Patients received a median dose of 16 Gy to the tumor margin. The median follow-up was 36 months (range 1-223 months). Results Overall tumor control was achieved in 93.4% of patients at last follow-up; actuarial tumor control was 98%, 95%, 91%, and 85% at 3, 5, 8, and 10 years postradiosurgery, respectively. Smaller adenoma volume (OR 1.08 [95% CI 1.02-1.13], p = 0.006) and absence of suprasellar extension (OR 2.10 [95% CI 0.96-4.61], p = 0.064) were associated with progression-free tumor survival. New or worsened hypopituitarism after radiosurgery was noted in 21% of patients, with thyroid and cortisol deficiencies reported as the most common postradiosurgery endocrinopathies. History of prior radiation therapy and greater tumor margin doses were predictive of new or worsening endocrinopathy after GKS. New or progressive cranial nerve deficits were noted in 9% of patients; 6.6% had worsening or new onset optic nerve dysfunction. In multivariate analysis, decreasing age, increasing volume, history of prior radiation therapy, and history of prior pituitary axis deficiency were predictive of new or worsening cranial nerve dysfunction. No patient died as a result of tumor progression. Favorable outcomes of tumor control and neurological preservation were reflected in a 4-point radiosurgical pituitary score. Conclusions Gamma Knife surgery is an effective and well-tolerated management strategy for the vast majority of patients with recurrent or residual nonfunctional pituitary adenomas. Delayed hypopituitarism is the most common complication after radiosurgery. Neurological and cranial nerve function were preserved in more than 90% of patients after radiosurgery. The radiosurgical pituitary score may predict outcomes for future patients who undergo GKS for a nonfunctioning adenoma.
Journal of Neurosurgery 04/2013; · 2.96 Impact Factor
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ABSTRACT: Object The appropriate management of unruptured intracranial arteriovenous malformations (AVMs) remains controversial. In the present study, the authors evaluate the radiographic and clinical outcomes of radiosurgery for a large cohort of patients with unruptured AVMs. Methods From a prospective database of 1204 cases of AVMs involving patients treated with radiosurgery at their institution, the authors identified 444 patients without evidence of rupture prior to radiosurgery. The patients' mean age was 36.9 years, and 50% were male. The mean AVM nidus volume was 4.2 cm(3), 13.5% of the AVMs were in a deep location, and 44.4% were at least Spetzler-Martin Grade III. The median radiosurgical prescription dose was 20 Gy. Univariate and multivariate Cox regression analyses were used to determine risk factors associated with obliteration, postradiosurgery hemorrhage, radiation-induced changes, and postradiosurgery cyst formation. The mean duration of radiological and clinical follow-up was 76 months and 86 months, respectively. Results The cumulative AVM obliteration rate was 62%, and the postradiosurgery annual hemorrhage rate was 1.6%. Radiation-induced changes were symptomatic in 13.7% and permanent in 2.0% of patients. The statistically significant independent positive predictors of obliteration were no preradiosurgery embolization (p < 0.001), increased prescription dose (p < 0.001), single draining vein (p < 0.001), radiological presence of radiation-induced changes (p = 0.004), and lower Spetzler-Martin grade (p = 0.016). Increased volume and higher Pittsburgh radiosurgery-based AVM score were predictors of postradiosurgery hemorrhage in the univariate analysis only. Clinical deterioration occurred in 30 patients (6.8%), more commonly in patients with postradiosurgery hemorrhage (p = 0.018). Conclusions Radiosurgery afforded a reasonable chance of obliteration of unruptured AVMs with relatively low rates of clinical and radiological complications.
Journal of Neurosurgery 03/2013; · 2.96 Impact Factor
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ABSTRACT: OBJECT: Gamma Knife radiosurgery (GKRS) is a minimally invasive technique employed in the treatment of intracranial arteriovenous malformations (AVM's). Patients experience a low incidence of complications following treatment. As the long-term follow-up data became available, some late adverse effects have been reported. However, the exact incidence of radiosurgically induced neoplasia is not known. METHODS: At UVA, imaging and clinical outcomes of 1309 patients with intracranial AVM's treated with GKRS have been reviewed. AVM patients underwent magnetic resonance imaging (MRI's) every 6 months for 2 years and then annually following GKRS. When the nidi were no longer visible on MRI, angiography was performed to verify the obliteration of AVM's. Patients were thereafter recommended to continue MRI's every 3-5 years to detect any long-term complications. A subset of 812, 358, and 78 patients had neuro-imaging and clinical follow-up of at least 3, 10, and 15 years respectively. RESULTS: The authors report the occurrence of 3 cases of radiosurgically induced neoplasia. More than 10 years after GKRS, 2 patients were found to have an incidental, uniformly enhancing, dural based mass lesion near the site of the AVM with radiological characteristics of a meningioma. As the lesions have shown no evidence of mass effect, they are being followed with serial neuro-imaging. A third patient was found to have neurological decline from a tumor in immediate proximity to an AVM previously treated with proton beam radiosurgery and GKRS. The patient underwent resection demonstrating a high grade glioma. The 3, 10, and 15-year incidence of a radiation-induced tumor is 0% (0/812), 0.3% (1/358), and 2.6% (2/78) respectively. The cumulative rate of radiosurgically induced tumors in those with a minimum of 10 year follow up is 3 in 4692 person-years or 64 in 100,000 person-years. Thus, patients had a 0.64% chance of developing a radiation induced tumor within 10 or more years following GKRS. If we calculate rates based on a subset of 78 patients with neuro-imaging and clinical follow-up of at least 15 years, the cumulative rate was 3.4%. These are the 2(nd), 3(rd), and 5(th) reported cases of radiation induced tumors following GKRS for an AVM. CONCLUSIONS: Although radiosurgery is generally considered a safe modality in the treatment of AVM's, radiation induced neoplasia is a rare but serious adverse event. The possibility of GKRS induced tumors underscores the necessity of long-term follow-up in AVM patients receiving radiosurgery.
World Neurosurgery 02/2013; · 0.68 Impact Factor
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ABSTRACT: The annual hemorrhage rate of intracranial arteriovenous malformations (AVMs) varies from 2 to 4%. In a patient with decades of life ahead, the cumulative risk of hemorrhage is significant. AVMs exhibiting characteristics such as deep venous drainage, venous stenosis, associated aneurysms and feeders from perforators are associated with an elevated risk of hemorrhage. We reviewed 1,400 AVM patients who underwent Gamma Knife surgery (GKS) at the University of Virginia between 1989 and 2009. The dose selection was based on the size and location of the nidus. The mean prescription dose was 21.2 Gy (range 5-36 Gy), and the mean maximum dose was 39.4 Gy (range 10-60 Gy). A total of 657 patients suffered 803 hemorrhagic events over 42,495 risk years before GKS. Assuming that these patients were at risk for hemorrhage since birth, the annual hemorrhage rate was 2.0%. If we calculate the hemorrhage rate after the diagnosis of the AVMs, the hemorrhage rate was 6.6%. Following GKS and prior to a radiographic documented obliteration, the annual hemorrhage rate was 2.5%; this rate is very similar to the 2.0% one computed prior to radiosurgery by assuming AVMs to be congenital. Once angiographic obliteration was confirmed after GKS, the hemorrhage rate dropped to zero.
Progress in neurological surgery 01/2013; 27:5-21.
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ABSTRACT: BACKGROUND:: Studies of new-onset Gamma Knife stereotactic radiosurgery (SRS) -induced hypopituitarism in large cohort of pituitary adenoma patients with long-term follow-up are lacking. OBJECTIVE:: We investigated the outcomes of SRS for pituitary adenoma patients with regard to newly developed hypopituitarism. METHODS:: This was a retrospective review of patients treated with SRS at the University of Virginia between 1994 and 2006. A total of 262 patients with a pituitary adenoma treated with SRS were reviewed. Thorough endocrine assessment was performed immediately prior to SRS and in regular follow-up. It consisted of 24-hour urine free cortisol (patients with Cushing's disease), serum ACTH, cortisol, FSH, LH, IGF-1, GH, testosterone (men), PRL, TSH, and free T4. RESULTS:: Endocrine remission occurred in 144 of 199 patients with a functioning adenoma. Tumor control rate was 89%. Eighty patients experienced at least one axis of new-onset SRS-induced hypopituitarism. The new hypopituitarism rate was 30% based upon endocrine follow-up ranging from 6 to 150 months; the actuarial rate of new pituitary hormone deficiency was 31.5% at 5 years post-SRS. On univariate and multivariate analyses, variables regarding the increased risk of hypopituitarism included suprasellar extension and higher radiation dose to the tumor margin; there were no correlations among tumor volume, prior transsphenoidal adenomectomy, prior RT, and age at SRS. CONCLUSION:: SRS provides an effective and safe treatment option for patients with a pituitary adenoma. Higher margin radiation dose to the adenoma and suprasellar extension were two independent predictors of SRS-induced hypopituitarism.
Neurosurgery 12/2012; · 2.79 Impact Factor
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ABSTRACT: Object The survival of patients with high-grade gliomas remains unfavorable. Mibefradil, a T-type calcium channel inhibitor capable of synchronizing dividing cells at the G1 phase, has demonstrated potential benefit in conjunction with chemotherapeutic agents for gliomas in in vitro studies. In vivo study of mibefradil and radiosurgery is lacking. The authors used an intracranial C6 glioma model in rats to study tumor response to mibefradil and radiosurgery. Methods Two weeks after implantation of C6 cells into the animals, each rat underwent MRI every 2 weeks thereafter for 8 weeks. After tumor was confirmed on MRI, the rats were randomly assigned to one of the experimental groups. Tumor volumes were measured on MR images. Experimental Group 1 received 30 mg/kg of mibefradil intraperitoneally 3 times a day for 1 week starting on postoperative day (POD) 15; Group 2 received 8 Gy of cranial radiation via radiosurgery delivered on POD 15; Group 3 underwent radiosurgery on POD 15, followed by 1 week of mibefradil; and Group 4 received mibefradil on POD 15 for 1 week, followed by radiosurgery sometime from POD 15 to POD 22. Twenty-seven glioma-bearing rats were analyzed. Survival was compared between groups using Kaplan-Meier methodology. Results Median survival in Groups 1, 2, 3, and 4 was 35, 31, 43, and 52 days, respectively (p = 0.036, log-rank test). Two animals in Group 4 survived to POD 60, which is twice the expected survival of untreated animals in this model. Analysis of variance and a post hoc test indicated no tumor volume differences on PODs 15 and 29. However, significant volume differences were found on POD 43; mean tumor volumes for Groups 1, 2, 3, and 4 were 250, 266, 167, and 34 mm(3), respectively (p = 0.046, ANOVA). A Cox proportional hazards regression test showed survival was associated with tumor volume on POD 29 (p = 0.001) rather than on POD 15 (p = 0.162). In vitro assays demonstrated an appreciable and dose-dependent increase in apoptosis between 2- and 7-μM concentrations of mibefradil. Conclusions Mibefradil response is schedule dependent and enhances survival and reduces glioblastoma when combined with ionizing radiation.
Journal of Neurosurgery 11/2012; · 2.96 Impact Factor
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ABSTRACT: Object Transcranial MR-guided focused ultrasound surgery (MRgFUS) is evolving as a treatment modality in neurosurgery. Until now, the trigeminal nerve was believed to be beyond the treatment envelope of existing high-frequency transcranial MRgFUS systems. In this study, the authors explore the feasibility of targeting the trigeminal nerve in a cadaveric model with temperature assessments using computer simulations and an in vitro skull phantom model fitted with thermocouples. Methods Six trigeminal nerves from 4 unpreserved cadavers were targeted in the first experiment. Preprocedural CT scanning of the head was performed to allow for a skull correction algorithm. Three-Tesla, volumetric, FIESTA MRI sequences were performed to delineate the trigeminal nerve and any vascular structures of the cisternal segment. The cadaver was positioned in a focused ultrasound transducer (650-kHz system, ExAblate Neuro, InSightec) so that the focus of the transducer was centered at the proximal trigeminal nerve, allowing for targeting of the root entry zone (REZ) and the cisternal segment. Real-time, 2D thermometry was performed during the 10- to 30-second sonication procedures. Post hoc MR thermometry was performed on a computer workstation at the conclusion of the procedure to analyze temperature effects at neuroanatomical areas of interest. Finally, the region of the trigeminal nerve was targeted in a gel phantom encased within a human cranium, and temperature changes in regions of interest in the skull base were measured using thermocouples. Results The trigeminal nerves were clearly identified in all cadavers for accurate targeting. Sequential sonications of 25-1500 W for 10-30 seconds were successfully performed along the length of the trigeminal nerve starting at the REZ. Real-time MR thermometry confirmed the temperature increase as a narrow focus of heating by a mean of 10°C. Postprocedural thermometry calculations and thermocouple experiments in a phantom skull were performed and confirmed minimal heating of adjacent structures including the skull base, cranial nerves, and cerebral vessels. For targeting, inclusion of no-pass regions through the petrous bone decreased collateral heating in the internal acoustic canal from 16.7°C without blocking to 5.7°C with blocking. Temperature at the REZ target decreased by 3.7°C with blocking. Similarly, for midcisternal targeting, collateral heating at the internal acoustic canal was improved from a 16.3°C increase to a 4.9°C increase. Blocking decreased the target temperature increase by 4.4°C for the same power settings. Conclusions This study demonstrates focal heating of up to 18°C in a cadaveric trigeminal nerve at the REZ and along the cisternal segment with transcranial MRgFUS. Significant heating of the skull base and surrounding neural structures did not occur with implementation of no-pass regions. However, in vivo studies are necessary to confirm the safety and efficacy of this potentially new, noninvasive treatment.
Journal of Neurosurgery 11/2012; · 2.96 Impact Factor
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ABSTRACT: Object The objective of this study was to evaluate the incidence, severity, clinical manifestations, and risk factors of radiation-induced imaging changes (RIICs) following Gamma Knife surgery (GKS) for cerebral arteriovenous malformations (AVMs). Methods A total of 1426 GKS procedures performed for AVMs with imaging follow-up available were analyzed. Radiation-induced imaging changes were defined as newly developed increased T2 signal surrounding the treated AVM nidi. A grading system was developed to categorize the severity of RIICs. Grade I RIICs were mild imaging changes imposing no mass effect on the surrounding brain. Grade II RIICs were moderate changes causing effacement of the sulci or compression of the ventricles. Grade III RIICs were severe changes causing midline shift of the brain. Univariate and multivariate logistic regression analyses were applied to test factors potentially affecting the occurrence, severity, and associated symptoms of RIICs. Results A total of 482 nidi (33.8%) developed RIICs following GKS, with 281 classified as Grade I, 164 as Grade II, and 37 as Grade III. The median duration from GKS to the development of RIICs was 13 months (range 2-124 months). The imaging changes disappeared completely within 2-128 months (median 22 months) following the development of RIICs. The RIICs were symptomatic in 122 patients, yielding an overall incidence of symptomatic RIICs of 8.6%. Twenty-six patients (1.8%) with RIICs had permanent deficits. A negative history of prior surgery, no prior hemorrhage, large nidus, and a single draining vein were associated with a higher risk of RIICs. Conclusions Radiation-induced imaging changes are the most common adverse effects following GKS. Fortunately, few of the RIICs are symptomatic and most of the symptoms are reversible. Patients with a relatively healthy brain and nidi that are large, or with a single draining vein, are more likely to develop RIICs.
Journal of Neurosurgery 11/2012; · 2.96 Impact Factor
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ABSTRACT: This article discusses contemporary use of external beam radiotherapy and stereotactic radiosurgery for pituitary adenoma patients. Specific techniques are discussed. In addition, indications and outcomes, including complications, are detailed.
Neurosurgery clinics of North America 10/2012; 23(4):571-86. · 1.73 Impact Factor
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ABSTRACT: : The practice of neurosurgery requires a thorough fund of knowledge. Residency and continuing medical education are designed to provide learning of relevant neurosurgical principles. Nevertheless, gaps in knowledge exist for neurosurgeons. This study examines the gaps in knowledge of neurosurgeons responding to SANS.
: From 2008 to 2010, 267 neurosurgery residents and 993 attending neurosurgeons completed the 245 available questions in SANS. Mean scores were calculated and assessed according to 18 major neurosurgical knowledge disciplines. Statistical analysis was carried out to evaluate for knowledge gaps amongst all users and differences in performance between residents and practicing neurosurgeons.
: The mean overall score was 66% ± 12%. Of the 18 major knowledge categories in SANS, respondents answered questions incorrectly 30% or greater of the time in half of the categories. Mean scores in anatomy 76% were the highest vs vascular 60% which were the lowest (P < .001). The mean score per category was significantly higher for practicing neurosurgeons 71.5% ± 8.9% than resident physicians 60.5 ± 12.6 (P < .001). Residents answered questions incorrectly 30% or greater of the time in all 18 categories vs 7 categories for attendings. Amongst residents the highest mean scores were achieved in anatomy and the lowest in vascular (P < .001); this differential response was also reflected amongst attending physicians.
: SANS demonstrated areas of knowledge gaps in a broad group of neurosurgeons. There were also significant differences between residents and attendings. Identification of areas of deficiency could prove useful in the design and implementation of educational programs.
Neurosurgery 08/2012; 71(2):E549. · 2.79 Impact Factor
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ABSTRACT: : The appropriate management of unruptured arteriovenous malformations (AVMs) remains the subject of controversy. In the present study, we evaluate the radiographic and clinical outcomes of Gamma Knife Radiosurgery (GKRS) for a large cohort of patients with unruptured AVMs.
: From a prospective database of 1204 AVM patients treated with GKRS at the University of Virginia from 1989 to 2009, we identified 444 patients with unruptured AVMs prior to treatment. The mean age was 36.9 years and 50% were male. The most common presenting symptoms were seizure (46.8%), headache (27.7%) and focal neurological deficit (11.9%). AVM characteristics were mean nidus volume was 4.2 cc, 13.5% deep location, and 44.4% at least Spetzler-Martin grade III. They were treated with GKRS using a median prescription dose of 20 Gy. Univariate and multivariate Cox regression analyses were used to determine risk factors associated with obliteration, post-GKRS hemorrhage, radiation-induced changes and post-GKRS cyst formation.
: The mean radiographic and clinical follow-ups were 75.5-85.5 months, respectively. The cumulative obliteration rate was 61.9% and the post-GKRS annual hemorrhage rate was 1.6% until and if obliteration occurred. Radiation-induced changes were symptomatic in 13.1% and permanent in 2.0% of patients. Statistically significant independent positive predictors of obliteration were no pre-GKRS embolization (P < 0.001), increased prescription dose (P < 0.001), single draining vein (P < 0.001), radiographic presence of radiation-induced changes (P = 0.004) and lower Spetzler-Martin grade (P = 0.016). Increased volume and higher Pittsburgh radiosurgery-based arteriovenous malformation (AVM) score were predictors of post-GKRS hemorrhage in the univariate but not in the multivariate analysis. Clinical deterioration occurred in 30 patients (6.8%) and was significantly more common in patients who had post-GKRS hemorrhage than in patients who did not (P = 0.018).
: GKRS afforded a reasonable chance of obliteration in unruptured AVMs. However, the benefits of successful obliteration must be weighed against the risk of post-GKRS hemorrhage and permanent clinical morbidity.
Neurosurgery 08/2012; 71(2):E545. · 2.79 Impact Factor
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ABSTRACT: : Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a novel combination of technologies that is actively being realized as a noninvasive therapeutic tool for a myriad of conditions. These applications are reviewed with a focus on neurological use. A combined search of PubMed and MEDLINE was performed to identify the key events and current status of MRgFUS, with a focus on neurological applications. MRgFUS signifies a potentially ideal device for the treatment of neurological diseases. As it is nearly real time, it allows monitored provision of treatment location and energy deposition; is noninvasive, thereby limiting or eliminating disruption of normal tissue; provides focal delivery of therapeutic agents; enhances radiation delivery; and permits modulation of neural function. Multiple clinical applications are currently in clinical use and many more are under active preclinical investigation. The therapeutic potential of MRgFUS is expanding rapidly. Although clinically in its infancy, preclinical and early-phase I clinical trials in neurosurgery suggest a promising future for MRgFUS. Further investigation is necessary to define its true potential and impact. ABBREVIATIONS:: BBB, blood-brain barrierHIFU, high-intensity focused ultrasoundMRgFUS, magnetic resonance-guided focused ultrasound surgerytPA, tissue plasminogen activator.
Neurosurgery 07/2012; 71(4):755-63. · 2.79 Impact Factor
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Jason P Sheehan,
Shota Tanaka,
Michael J Link,
Bruce E Pollock,
Douglas Kondziolka,
David Mathieu,
Christopher Duma,
A Byron Young,
Anthony M Kaufmann,
Heyoung McBride,
Peter A Weisskopf,
Zhiyuan Xu,
Hideyuki Kano,
Huai-che Yang,
L Dade Lunsford
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ABSTRACT: Glomus tumors are rare skull base neoplasms that frequently involve critical cerebrovascular structures and lower cranial nerves. Complete resection is often difficult and may increase cranial nerve deficits. Stereotactic radiosurgery has gained an increasing role in the management of glomus tumors. The authors of this study examine the outcomes after radiosurgery in a large, multicenter patient population.
Under the auspices of the North American Gamma Knife Consortium, 8 Gamma Knife surgery centers that treat glomus tumors combined their outcome data retrospectively. One hundred thirty-four patient procedures were included in the study (134 procedures in 132 patients, with each procedure being analyzed separately). Prior resection was performed in 51 patients, and prior fractionated external beam radiotherapy was performed in 6 patients. The patients' median age at the time of radiosurgery was 59 years. Forty percent had pulsatile tinnitus at the time of radiosurgery. The median dose to the tumor margin was 15 Gy. The median duration of follow-up was 50.5 months (range 5-220 months).
Overall tumor control was achieved in 93% of patients at last follow-up; actuarial tumor control was 88% at 5 years postradiosurgery. Absence of trigeminal nerve dysfunction at the time of radiosurgery (p = 0.001) and higher number of isocenters (p = 0.005) were statistically associated with tumor progression-free tumor survival. Patients demonstrating new or progressive cranial nerve deficits were also likely to demonstrate tumor progression (p = 0.002). Pulsatile tinnitus improved in 49% of patients who reported it at presentation. New or progressive cranial nerve deficits were noted in 15% of patients; improvement in preexisting cranial nerve deficits was observed in 11% of patients. No patient died as a result of tumor progression.
Gamma Knife surgery was a well-tolerated management strategy that provided a high rate of long-term glomus tumor control. Symptomatic tinnitus improved in almost one-half of the patients. Overall neurological status and cranial nerve function were preserved or improved in the vast majority of patients after radiosurgery.
Journal of Neurosurgery 06/2012; 117(2):246-54. · 2.96 Impact Factor
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ABSTRACT: Nonfunctioning pituitary macroadenomas often recur after microsurgery and thereby require further treatment. Gamma Knife surgery (GKS) has been used to treat recurrent adenomas. In this study, the authors evaluated outcomes following GKS of nonfunctioning pituitary macroadenomas and assessed predictors of tumor control, neurological deficits, and delayed hypopituitarism.
Between June 1989 and March 2010, 140 consecutive patients with nonfunctioning pituitary macroadenomas were treated using GKS at the University of Virginia. The median patient age was 51 years (range 21-82 years), and 56% of patients were male. Mean tumor volume was 5.6 cm3 (range 0.6-35 cm3). Thirteen patients were treated with GKS as primary therapy, and 127 had undergone at least 1 open resection prior to GKS. Ninety-three patients had a history of hormone therapy prior to GKS. The mean maximal dose of GKS was 38.6 Gy (range 10-70 Gy), the mean marginal dose was 18 Gy (range 5-25 Gy), and the mean number of isocenters was 9.8 (range 1-26). Follow-up evaluations were performed in all 140 patients, ranging from 0.5 to 17 years (mean 5 years, median 4.2 years).
Tumor volume remained stable or decreased in 113 (90%) of 125 patients with available follow-up imaging. Kaplan-Meier analysis demonstrated radiographic progression free survival at 2, 5, 8, and 10 years to be 98%, 97%, 91%, and 87%, respectively. In multivariate analysis, a tumor volume greater than 5 cm3 (hazard ratio=5.0, 95% CI 1.5-17.2; p=0.023) was the only factor predictive of tumor growth. The median time to tumor progression was 14.5 years. Delayed hypopituitarism occurred in 30.3% of patients. No factor was predictive of post-GKS hypopituitarism. A new or worsening cranial nerve deficit occurred in 16 (13.7%) of 117 patients. Visual decline was the most common neurological deficit (12.8%), and all patients experiencing visual decline had evidence of tumor progression. In multivariate analysis, a tumor volume greater than 5 cm3 (OR=3.7, 95% CI 1.2-11.7; p=0.025) and pre-GKS hypopituitarism (OR=7.5, 95% CI 1.1-60.8; p=0.05) were predictive of a new or worsened neurological deficit.
In patients with nonfunctioning pituitary macroadenomas, GKS confers a high rate of tumor control and a low rate of neurological deficits. The most common complication following GKS is delayed hypopituitarism, and this occurs in a minority of patients.
Journal of Neurosurgery 05/2012; 117(1):129-35. · 2.96 Impact Factor
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ABSTRACT: Gamma Knife surgery (GKS) has become a significant component of neurosurgical treatment for recurrent secretory and nonsecretory pituitary adenomas. Although the long-term risks of visual dysfunction following microsurgical resection of pituitary adenomas has been well studied, the comparable risk following radiosurgery is not well defined. This study evaluates the long-term risks of ophthalmological dysfunction following GKS for recurrent pituitary adenomas.
An analysis of 217 patients with recurrent secretory (n = 131) and nonsecretory (n = 86) pituitary adenomas was performed to determine the incidence of and risk factors for subsequent development of visual dysfunction. Patients underwent ophthalmological evaluation as part of post-GKS follow-up to assess for new or worsened cranial nerve II, III, IV, or VI palsies. The median follow-up duration was 32 months. The median maximal dose was 50 Gy, and the median peripheral dose was 23 Gy. A univariate analysis was performed to assess for risk factors of visual dysfunction post-GKS.
Nine patients (4%) developed new visual dysfunctions, and these occurred within 6 hours to 34 months following radiosurgery. None of these 9 patients had tumor growth on post-GKS neuroimaging studies. Three of these patients had permanent deficits whereas in 6 the deficits resolved. Five of the 9 patients had prior GKS or radiotherapy, which resulted in a significant increase in the incidence of cranial nerve dysfunction (p = 0.0008). An increased number of isocenters (7.1 vs 5.0, p = 0.048) was statistically related to the development of visual dysfunction. Maximal dose, margin dose, optic apparatus dose, tumor volume, cavernous sinus involvement, and suprasellar extension were not significantly related to visual dysfunction (p >0.05).
Neurological and ophthalmological assessment in addition to routine neuroimaging and endocrinological follow-up are important to perform following GKS. Patients with a history of radiosurgery or radiation therapy are at higher risk of cranial nerve deficits. Also, a reduction in the number of isocenters delivered, along with volume treated, particularly in the patients with secretory tumors, appears to be the most reasonable strategy to minimize the risk to the visual system when treating recurrent pituitary adenomas with stereotactic radiosurgery.
Journal of Neurosurgery 03/2012; 116(6):1304-10. · 2.96 Impact Factor
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ABSTRACT: The authors present a case of an arteriovenous malformation of the central sulcus treated with Gamma Knife surgery. The patient developed perilesional edema 9 months after treatment and experienced severe headache and hemiparesis. Her symptoms were refractory to corticosteroid therapy and pain management. She was subsequently treated with bevacizumab with striking improvement in her symptoms and results of neuroimaging studies. This is the first time that bevacizumab has been used to control severe refractory perilesional edema related to an intracranial arteriovenous malformation.
Journal of Neurosurgery 02/2012; 116(5):972-7. · 2.96 Impact Factor
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ABSTRACT: Gamma Knife surgery (GKS) has emerged as the treatment of choice for small- to medium-sized cerebral arteriovenous malformations (AVMs) in deep locations. The present study aims to investigate the outcomes of GKS for AVMs in the basal ganglia and thalamus.
Between 1989 and 2007, 85 patients with AVMs in the basal ganglia and 97 in the thalamus underwent GKS and were followed up for more than 2 years. The nidus volumes ranged from 0.1 to 29.4 cm(3) (mean 3.4 cm(3)). The mean margin dose at the initial GKS was 21.3 Gy (range 10-28 Gy). Thirty-six patients underwent repeat GKS for residual AVMs at a median 4 years after initial GKS. The mean margin dose at repeat GKS was 21.1 Gy (range 7.5-27 Gy).
Following a single GKS, total obliteration of the nidus was confirmed on angiograms in 91 patients (50%). In 12 patients (6.6%) a subtotal obliteration was achieved. No flow voids were observed on MR imaging in 14 patients (7.7%). Following single or repeat GKS, total obliteration was angiographically confirmed in 106 patients (58.2%) and subtotal obliteration in 8 patients (4.4%). No flow voids on MR imaging were observed in 18 patients (9.9%). The overall obliteration rates following one or multiple GKSs based on MR imaging or angiography was 68%. A small nidus volume, high margin dose, low number of isocenters, and no history of embolization were significantly associated with an increased rate of obliteration. Twenty-one patients experienced 25 episodes of hemorrhage in 850 risk-years following GKS, yielding an annual hemorrhage rate of 2.9%. Four patients died in this series: 2 due to complications of hemorrhage and 2 due to unrelated diseases. Permanent neurological deficits caused by radiation were noted in 9 patients (4.9%).
Gamma Knife surgery offers a reasonable chance of obliterating basal ganglia and thalamic AVMs and does so with a low risk of complications. It is an optimal treatment option in patients for whom the anticipated risk of microsurgery is too high.
Journal of Neurosurgery 01/2012; 116(4):899-908. · 2.96 Impact Factor
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ABSTRACT: Skull base meningiomas are challenging tumors owing in part to their close proximity to important neurovascular structures. Complete microsurgical resection can be associated with significant morbidity, and recurrence rates are not inconsequential. In this study, the authors evaluate the outcomes of skull base meningiomas treated with Gamma Knife surgery (GKS) both as an adjunct to microsurgery and as a primary treatment modality.
The authors performed a retrospective review of a prospectively compiled database detailing the outcomes in 255 patients with skull base meningiomas treated at the University of Virginia from 1989 to 2006. All patients had a minimum follow-up of 24 months. The group comprised 54 male and 201 female patients, with a median age of 55 years (range 19-85 years). One hundred nine patients were treated with upfront radiosurgery, and 146 patients were treated with GKS following resection. Patients were assessed clinically and radiographically at routine intervals following GKS. Factors predictive of new neurological deficit following GKS were assessed via univariate and multivariate analysis, and Kaplan-Meier analysis and Cox multivariate regression analysis were used to assess factors predictive of tumor progression.
Meningiomas were centered over the cerebellopontine angle in 43 patients (17%), the clivus in 40 (16%), the petroclival region in 28 (11%), the petrous region in 6 (2%), and the parasellar region in 138 (54%). The median duration of follow-up was 6.5 years (range 2-18 years). The mean preradiosurgery tumor volume was 5.0 cm(3) (range 0.3-54.8 cm(3)). At most recent follow-up, 220 patients (86%) displayed either no change or a decrease in tumor volume, and 35 (14%) displayed an increase in volume. Actuarial progression-free survival at 3, 5, and 10 years was 99%, 96%, and 79%, respectively. In Cox multivariate analysis, pre-GKS covariates associated with tumor progression included age greater then 65 years (HR 3.41, 95% CI 1.63-7.13, p = 0.001) and decreasing dose to tumor margin (HR 0.90, 95% CI 0.80-1.00, p = 0.05). At most recent clinical follow-up, 230 patients (90%) demonstrated no change or improvement in their neurological condition and the condition of 25 patients had deteriorated (10%). In multivariate analysis, the factors predictive of new or worsening symptoms were increasing duration of follow-up (OR 1.01, 95% CI 1.00-1.02, p = 0.015), tumor progression (OR 2.91, 95% CI 1.60-5.31, p < 0.001), decreasing maximum dose (OR 0.90, 95% CI 0.84-0.97, p = 0.007), and petrous or clival location versus parasellar, petroclival, and cerebellopontine angle location (OR 3.47, 95% CI 1.23-9.74, p = 0.018).
Stereotactic radiosurgery offers a high rate of tumor control and neurological preservation in patients with skull base meningiomas. After radiosurgery, better outcomes were observed for those receiving an optimal radiosurgery dose and harboring tumors located in a cerebellopontine angle, parasellar, or petroclival location.
Journal of Neurosurgery 12/2011; 116(3):588-97. · 2.96 Impact Factor
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ABSTRACT: We evaluated the effects of gamma-knife radiosurgery (GKRS) on the cognitive functioning of patients with a pituitary adenoma.
A total of 14 patients with pituitary adenomas were enrolled in this neurocognitive study. Nine patients had Cushing disease, and five had nonfunctioning pituitary adenomas. Five patients underwent GKRS for their pituitary adenomas. Other treatment modalities included transsphenoidal resection and conservative management. Comparisons were made between treatment groups and between those with Cushing disease versus those with a nonfunctioning adenoma by the use of psychometric tests of general intellectual functioning, memory, and current mood state. These tests were the Symptom Checklist 90 Revised, Wechsler Test of Adult Reading, Wechsler Memory Scale-third edition, selected subtests of the Wechsler Adult Intelligence Scale-third edition, and the Delis-Kaplan Executive Function System.
When analyzed collectively, the patient group showed deficits in immediate memory (t=-2.70, P=0.02) and high levels of psychological distress (46% of patients) in the presence of intact general intellectual functioning. No neurocognitive differences were found between the GKRS treated group versus participants not treated with GKRS (t≤0.70, P≥0.39). Similarly, no appreciable neurocognitive differences were demonstrated between those with nonfunctioning adenomas as compared with those with Cushing disease (t≤1.56, P≥0.15).
We found no evidence that GKRS impairs the neurocognitive functioning of patients with pituitary disease above any impairment caused by the disease itself. Further studies will require approximately 20 patients in each comparison group to confirm this result.
World Neurosurgery 11/2011; 78(1-2):122-8. · 0.68 Impact Factor
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ABSTRACT: Trigeminal neuralgia is characterized by a temporary paroxysmal lancinating facial pain in the trigeminal nerve distribution. The prevalence is four to five per 100,000. Local pressure on nerve fibers from vascular loops results in painful afferent discharge from an injured segment of the fifth cranial nerve. Microvascular decompression addresses the underlying pathophysiology of the disease, making this treatment the gold standard for medically refractory trigeminal neuralgia. In patients who cannot tolerate a surgical procedure, those in whom a vascular etiology cannot be identified, or those unwilling to undergo an open surgery, stereotactic radiosurgery is an appropriate alternative. The majority of patients with typical facial pain will achieve relief following radiosurgical treatment. Long-term follow-up for recurrence as well as for radiation-induced complications is required in all patients undergoing stereotactic radiosurgery for trigeminal neuralgia.
Expert Review of Medical Devices 11/2011; 8(6):709-21. · 2.63 Impact Factor
