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adiosurgery is aminimally invasive technique designed by Lars Leksell to deliver a destructive amount of radiation to R intracranial lesions that may be inaccessible or unsuitable for open surgery. Undoubtedly, the experiences of delivering ether anesthesia to neurosurgical patients for Dr. Olivecrona motivated Leksell to develop a techniquewith fewer complications than open surgery. A passage from Leksell’s autobiography proved the idea of a minimally invasive neurosurgical approach as on his mind for some time. At the first Scandinavian neurosurgical meeting held in Oslo, Leksell left the conference room during a less-than-exciting presentation and decided to walk in a garden. While on this walk, Leksell met Sir HughCairns. Leksell confessed to Cairns his doubts concerning the state of neurosurgical techniques available at the time and was convinced that something new had to be developed. He explained his plans to mechanically direct a probe into the brain using perhaps the brain’s own electrical activity and ablate pain pathways. He also mused about the idea of using narrow-beam X-ray or ultrasound as the physical agent and doing away with the probe entirely. His enthusiasm and ideas were given a warm reception by Cairns, and the encouraged young Leksell beganwork that led to the development of an “arc-radius” type stereotactic system. Leksell wrote, “I was born under the sign of the ‘archer’ and looked forward to sharpshoot into the brain” (39).

BACKGROUND The effectiveness and risk of gamma knife surgery (GKS) in the management of partially embolized cerebral arteriovenous malformations (AVMs) remain to be elucidated. OBJECTIVE To evaluate the long-term imaging and clinical outcomes of GKS in AVM patients who had undergone previous partial embolization and compare the results with patients treated with GKS alone. METHODS A total of 215 embolized AVMs were analyzed. The mean patient age was 32.9 years. The mean volume of the nidus was 4.6 mL (range, 0.1-29.4 mL), and the mean prescription dose was 19.6 Gy (range, 4-28 Gy). This group was compared with 729 nonembolized AVMs. RESULTS After embolization and GKS, angiographically confirmed total obliteration of the AVMs was significantly lower (33%) compared with patients in whom GKS was used alone (60.9%; P

Objective To evaluate the long-term imaging and clinical outcomes of patients with brainstem arteriovenous malformations (AVMs) treated with Gamma Knife surgery (GKS). Methods The study included 85 patients with brainstem AVMs undergoing GKS during the period 1989–2007. The locations of the nidi were the midbrain in 42 patients, pons in 31 patients, and medulla oblongata in 12 patients. The volume of the nidi ranged from 0.1–8.9 mL (median 1.4 mL, mean 1.9 mL), and the prescription dose ranged from 5–32 Gy (median 20 Gy, mean 19.9 Gy). After the initial Gamma procedure, 18 patients had repeat GKS for AVM residuals that were still patent. Two patients had a third GKS 7 years and 16 years after a failed repeat GKS. Clinical follow-up ranged from 24–252 months with a mean of 100 months (median 102 months) after the initial GKS. Results GKS yielded a total angiographic obliteration in 50 (58.8%) patients and subtotal obliteration in 4 (4.7%) patients. In 22 (25.9%) patients, the AVMs remained patent. In 9 patients (10.6%), no flow voids were observed on magnetic resonance imaging (MRI), but angiographic confirmation was unavailable. A small nidus volume and a high prescription dose were significantly associated with increased AVM obliteration rate. Radiation-induced changes developed in 34 patients (40%); 24 were asymptomatic, 1 patient had only headache, and 9 patients developed neurologic deficits. One patient developed a large cyst 6 years after GKS. Conclusions Given the poor surgical outcome of brainstem AVMs, the results of 59% nidus obliteration and 6% permanent neurologic deficits make GKS a reasonable management of these difficult lesions.

Object Gamma Knife surgery (GKS) is a common treatment for recurrent or residual pituitary adenomas. This study evaluates a large cohort of patients with a pituitary adenoma to characterize factors related to endocrine remission, control of tumor growth, and development of pituitary deficiency. Methods A total of 418 patients who underwent GKS with a minimum follow-up of 6 months (median 31 months) and for whom there was complete follow-up were evaluated. Statistical analysis was performed to evaluate for significant factors (p < 0.05) related to treatment outcomes. Results In patients with a secretory pituitary adenoma, the median time to endocrine remission was 48.9 months. The tumor margin radiation dose was inversely correlated with time to endocrine remission. Smaller adenoma volume correlated with improved endocrine remission in those with secretory adenomas. Cessation of pituitary suppressive medications at the time of GKS had a trend toward statistical significance in regard to influencing endocrine remission. In 90.3% of patients there was tumor control. A higher margin radiation dose significantly affected control of adenoma growth. New onset of a pituitary hormone deficiency following GKS was seen in 24.4% of patients. Treatment with pituitary hormone suppressive medication at the time of GKS, a prior craniotomy, and larger adenoma volume at the time of radiosurgery were significantly related to loss of pituitary function. Conclusions Smaller adenoma volume improves the probability of endocrine remission and lowers the risk of new pituitary hormone deficiency with GKS. A higher margin dose offers a greater chance of endocrine remission and control of tumor growth.

Background Increased signals on T2-weighted magnetic resonance imaging usually interpreted as radiation-induced changes or brain edema is a common short- to mid-term complication after Gamma Knife surgery (GKS) for intracranial arteriovenous malformations (AVMs), although its nature remains to be clarified. Early draining vein occlusion with resultant brain edema or hemorrhage, although well established in surgical series, was not described in radiosurgical literature until recently. Objective To outline the incidence, clinical manifestations, and outcomes of this unusual complication in our series of 1256 AVM patients treated with GKS. Methods From 1989 to 2008, 1400 patients underwent GKS for cerebral AVMs or dural arteriovenous fistulae at the University of Virginia. In 1256 patients, magnetic resonance imaging after GKS was available for analysis of radiation-induced changes and early draining vein occlusion. Results After GKS, 456 patients (36%) developed radiation-induced changes surrounding the treated nidi. Among these patients, 12 had early thrombosis of the draining vein accompanied by radiation-induced changes. Venous thrombosis occurred 6 to 25 months (median 11.6 months) after GKS. Three patients were asymptomatic on the image findings of venous occlusion and brain edema, 3 experienced headache, 1 had seizure and headache, and neurological deficits developed in 5. Patients with neurological deficits were treated with corticosteroids; 2 of the patients recovered completely, 1 still had slight hemiparesis, 1 had short-term memory deficits, and 1 died of massive intracerebral hemorrhage. Conclusion Although venous structures are considered more radioresistant, endothelial damage accompanied by venous flow stasis might cause early venous thrombosis and premature venous occlusion after radiosurgery for AVMs. In our series, all patients had a favorable outcome except 1 with a fatal hemorrhage.

BACKGROUND: Circadian cell-cycle progression causes fluctuating radiosensitivity in many tissues, which could affect clinical outcomes. The purpose of this study was to determine whether outcomes of single-session gamma knife radiosurgery (GKRS) for metastatic nonsmall cell lung cancer (NSCLC) differ based on treatment time. METHODS: Fifty-eight patients received GKRS between 10:00 am and 12:30 pm and 39 patients received GKRS between 12:30 pm and 3:00 pm. The mean peripheral dose was 18.6 Gy. The mean tumor size was 7.3 cm3. Magnetic resonance imaging was used to score local control at 3 months. Cause of death (COD) was categorized as central nervous system (CNS)-related or systemic. RESULTS: Demographic and disease characteristics of the 2 groups were similar. Local control at 3 months was achieved in 97% (35/36) of patients who underwent GKRS early in the day versus 67% (8/12) of patients who underwent GKRS later in the day (chi-square, P = .014). Early GKRS was associated with better survival (median 9.5 months) than late GKRS (median 5 months) (Kaplan-Meier log-rank test, P = .025). Factors contributing to better survival in a Cox regression model included early treatment time (P = .004) and recursive partition analysis class (P < .001). Cause of death in the early treatment group was CNS-related in 6% (3/47) of patients versus 24% (8/34) of patients in the late treatment group (chi-square test, P = .026). CONCLUSIONS: GKRS for metastatic NSCLC had better local control, better survival, and a lower rate of CNS-related cause of death when given earlier in the day versus later in the day. These retrospective data should encourage future study in brain radiosurgery and non-CNS stereotactic body radiotherapy series. Cancer 2011. © 2010 American Cancer Society.

The field of magnetic resonance imaging-guided high-intensity focused ultrasound surgery (MRgFUS) is a rapidly evolving one, with many potential applications in neurosurgery. The first of 3 articles on MRgFUS, this article focuses on the historical development of the technology and its potential applications in modern neurosurgery. The evolution of MRgFUS has occurred in parallel with modern neurological surgery, and the 2 seemingly distinct disciplines share many of the same pioneering figures. Early studies on focused ultrasound treatment in the 1940s and 1950s demonstrated the ability to perform precise lesioning in the human brain, with a favorable risk-benefit profile. However, the need for a craniotomy, as well as the lack of sophisticated imaging technology, resulted in limited growth of high-intensity focused ultrasound for neurosurgery. More recently, technological advances have permitted the combination of high-intensity focused ultrasound along with magnetic resonance imaging guidance to provide an opportunity to effectively treat a variety of central nervous system disorders. Although challenges remain, high-intensity focused ultrasound-mediated neurosurgery may offer the ability to target and treat central nervous system conditions that were previously extremely difficult to address. The remaining 2 articles in this series will focus on the physical principles of modern MRgFUS as well as current and future avenues for investigation.

Object Although considered benign tumors, neurocytomas have various biological behaviors, histological patterns, and clinical courses. In the last 15 years, fractionated radiotherapy and radiosurgery in addition to microsurgery have been used in their management. In this study, the authors present their experience using Gamma Knife surgery (GKS) in the treatment of these tumors. Methods Between 1989 and 2004, the authors performed GKS in seven patients with a total of nine neurocytomas. Three patients harbored five recurrent tumors after a gross-total resection, three had progression of previous partially resected tumors, and one had undergone a tumor biopsy only. The mean tumor volume at the time of GKS ranged from 1.4 to 19.8 cm3 (mean 6.0 cm3). A mean peripheral dose of 16 Gy was prescribed to the tumor margin with the median isodose configuration of 32.5%. Results After a mean follow-up period of 60 months, four of the nine tumors treated disappeared and four shrank significantly. Because of secondary hemorrhage, an accurate tumor volume could not be determined in one. Four patients were asymptomatic during the follow-up period, and the condition of the patient who had residual hemiparesis from a previous transcortical resection of the tumor was stable. Additionally, the patient who experienced tumor hemorrhage required a shunt revision, and another patient died of sepsis due to a shunt infection. Conclusions Based on this limited experience, GKS seems to be an appropriate management alternative. It offers control over the tumor with the benefits of minimal invasiveness and low morbidity rates. Recurrence, however, is not unusual following both microsurgery and GKS. Open-ended follow-up imaging is required to detect early recurrence and determine the need for retreatment.

Object Patients with adrenocorticotropic hormone (ACTH)–secreting pituitary adenomas may require a bilateral adrenalectomy to treat their Cushing's disease. Approximately one third of these patients, however, will experience progressive enlargement of the residual pituitary adenoma, develop hyperpigmentation, and have an elevated level of serum ACTH. These patients with Nelson's syndrome can be treated with Gamma Knife surgery (GKS). Methods The prospectively collected University of Virginia Gamma Knife database of patients with pituitary adenomas was reviewed to identify all individuals with Nelson's syndrome who were treated with GKS. Twenty-three patients with a minimum of 6 months of follow up were identified in the database. These patients were assessed for tumor control (that is, lack of tumor growth over time) with neuroimaging studies (median follow-up duration 22 months) and for biochemical normalization of their ACTH levels (median follow-up duration 50 months). Neuroimaging follow-up studies were available for 22 patients, and endocrine follow up was available for 15 patients in whom elevation of ACTH levels was documented prior to GKS. In the 22 patients in whom neuroimaging follow-up studies were available, 12 had a decrease in tumor size, eight had no tumor growth, and two had an increase in tumor volume. Ten of 15 patients with elevated ACTH levels prior to GKS showed a decrease in their ACTH levels at last follow up; three of these 10 patients achieved normal ACTH levels (< 50 pg/ml) and the other five patients with initially elevated values had an increase in ACTH levels. Ten patients were thoroughly evaluated for post-GKS pituitary function; four were found to have new pituitary hormone deficiency and six did not have hypopituitarism after GKS. One patient suffered a permanent third cranial nerve palsy and four patients are now deceased. Conclusions Gamma Knife surgery may control the residual pituitary adenoma and decrease ACTH levels in patients with Nelson's syndrome. Delayed hypopituitarism or cranial nerve palsies can occur after GKS. Patients with Nelson's syndrome require continued multidisciplinary follow-up care. Given the difficulties associated with management of Nelson's syndrome, even the modest results of GKS may be helpful for a number of patients.

Object Trigeminal schwannomas are rare intracranial tumors. In the past, resection and radiation therapy were the mainstays of their treatment. More recently, neurosurgeons have begun to use radiosurgery in the treatment of trigeminal schwannomas because of its successful use in the treatment of vestibular schwannomas. In this article the authors evaluate the radiological and clinical outcomes in a series of patients in whom Gamma Knife surgery (GKS) was used to treat trigeminal schwannomas. Methods Twenty-six patients with trigeminal schwannomas underwent GKS at the University of Virginia Lars Lek-sell Gamma Knife Center between 1989 and 2005. Five of these patients had neurofibromatosis and one patient was lost to follow up. The median tumor volume was 3.96 cm3, and the mean follow-up period was 48.5 months. The median prescription radiation dose was 15 Gy, and the median prescription isodose configuration was 50%. There was clinical improvement in 18 patients (72%), a stable lesion in four patients (16%), and worsening of the disease in three patients (12%). On imaging, the schwannomas shrank in 12 patients (48%), remained stable in 10 patients (40%), and increased in size in three patients (12%). These results were comparable for primary and adjuvant GKSs. No tumor growth following GKS was observed in the patients with neurofibromatosis. Conclusions Gamma Knife surgery affords a favorable risk-to-benefit profile for patients harboring trigeminal schwannomas. Larger studies with open-ended follow-up review will be necessary to determine the long-term results and complications of GKS in the treatment of trigeminal schwannomas.

Object Subtotal obliteration of cerebral arteriovenous malformations (AVMs) after Gamma Knife surgery (GKS) implies a complete angiographic disappearance of the AVM nidus but persistence of an early filling draining vein, indicating that residual shunting is still present; hence, per definition there is still a patent AVM and the risk of bleeding is not eliminated. The aim of this study was to determine the risk of hemorrhage for patients with subtotal obliteration of AVMs. Methods After GKS for cerebral AVMs, follow-up angiography demonstrated a subtotally obliterated lesion in 159 patients. Of these, in 16 patients a subtotally obliterated AVM developed after a second GKS was performed for the partially obliterated lesion. The mean age of these patients was 35.2 years at the time of the diagnosis of subtotally obliterated AVMs. The lesion volumes at the time of initial GKS treatment ranged from 0.1 to 11.5 cm3 (mean 2.5 cm3). The mean peripheral dose used in the 175 GKS treatments was 22.5 Gy (median 23 Gy, range 15–31 Gy). To achieve total obliteration of the AVM, 23 patients underwent a new GKS targeting the proximal end of the early filling vein. The mean peripheral dose given in these cases was 23 Gy (median 24, range 18–25 Gy). The incidence of subtotally obliterated AVMs was 7.6% from a total of 2093 AVMs treated and in which follow-up imaging was available. The diagnosis of subtotally obliterated AVMs was made a mean of 29.4 months (range 4–178 months) after GKS. The number of patient-years at risk (from the time of the diagnosis of subtotally obliterated AVMs until either the confirmation of a total obliteration of the lesion on angiography or the time of the latest follow-up angio-graphic study that still visualized the early filling vein) was a mean of 3.9 years, ranging from 0.5 to 13.5 years, and a total of 601 patient-years. There was no case of bleeding after the diagnosis of subtotally obliterated AVMs. Of 90 patients who did not undergo further treatment and in whom follow-up angiography studies were available, the same early filling veins still filled in 24 (26.7%), and the subtotally obliterated AVMs were subsequently obliterated in 66 patients (73.3%). In 19 patients who underwent repeated GKS for subtotally obliterated AVMs and in whom follow-up angiography studies were available, the AVMs were obliterated in 15 (78.9%) and remained patent in four (21.1%). Conclusions The fact that none of the patients with subtotally obliterated AVMs suffered a rupture is not compatible with the assumption of an unchanged risk of hemorrhage for these lesions, and implies that the protection from re-bleeding in patients with subtotal obliteration is significant. Subtotal obliteration does not necessarily seem to be a stage of an ongoing obliteration. At least in some cases it represents an end point of this process, with no subsequent obliteration occurring. This observation requires further confirmation by open-ended follow-up imaging.

Object The authors report on a retrospective analysis of the imaging and clinical outcomes following gamma surgery in 100 patients with nonsecretory pituitary macroadenoma. Methods Between June 1989 and March 2004, 100 consecutive patients with nonsecretory pituitary macroadenoma were treated at the Lars Leksell Center for Gamma Surgery, University of Virginia Health System (Charlottesville, VA). Ninety-two patients had residual or recurrent macroadenoma following one or more surgical procedures. In eight patients, gamma surgery was the primary treatment. Ten patients received conventional fractionated radiotherapy before the gamma surgery. Sixty-nine patients required hormone replacement therapy for one or more deficits before gamma knife treatment. Peripheral doses between 5 and 25 Gy (mean 18.5 Gy) were administered. Imaging and endocrinological follow-up evaluations were performed in 90 patients; these studies ranged from 6 to 142 months (mean 44.9 months) and 6 to 127 months (mean 47.9 months), respectively. Tumor volume decreased in 59 patients (65.6%), remained unchanged in 24 (26.7%), and increased in seven (7.8%). The minimal effective peripheral dose was 12 Gy; peripheral doses greater than 20 Gy did not seem to provide additional benefit. Of 61 patients with a partially or fully functioning pituitary gland and follow-up data, 12 (19.7%) suffered new hormone deficits following gamma surgery. In patients with endocrinological follow-up data that had been collected over more than 2 years, the rate of new deficits was 25%. No neurological morbidity or death was related to treatment. Conclusions Current experience suggests that gamma surgery is an appropriate means of managing recurrent or residual nonsecretory pituitary macroadenoma following microsurgery and a primary treatment in selected patients. To evaluate definite rates of recurrence and new endocrine deficiencies, long-term follow-up studies are needed.

Object. Microvascular decompression (MVD) and percutaneous ablation surgery have historically been the treatments of choice for medically refractory trigeminal neuralgia (TN). Gamma knife surgery (GKS) has been used as an alternative, minimally invasive treatment in TN. In the present study, the authors evaluated the long-term results of GKS in the treatment of TN. Methods. From 1996 to 2003, 151 cases of TN were treated with GKS. In this group, radiosurgery was performed once in 136 patients, twice in 14 patients, and three times in one patient. The types of TN were as follows: 122 patients with typical TN, three with atypical TN, four with multiple sclerosis—associated TN, and seven with TN and a history of a cavernous sinus tumor. In each case, the chosen radiosurgical target was located 2 to 4 mm anterior to the entry of the trigeminal nerve into the pons. The maximal radiation doses ranged from 50 to 90 Gy. The median age of the patients was 68 years (range 22–90 years), and the median time from diagnosis to GKS was 72 months (range 1–276 months). The median follow up was 19 months (range 2–96 months). Clinical outcomes and postradiosurgical magnetic resonance (MR) imaging studies were analyzed. Univariate and multivariate analyses were performed to evaluate factors that correlated with a favorable, pain-free outcome. The mean time to relief of pain was 24 days (range 1–180 days). Forty-seven, 45, and 34% of patients were pain free without medication at the 1-, 2-, and 3-year follow ups, respectively. Ninety, 77, and 70% of patients experienced some improvement in pain at the 1-, 2-, and 3-year follow ups, respectively. Thirty-three (27%) of 122 patients with initial improvement subsequently experienced pain recurrence a median of 12 months (range 2–34 months) post-GKS. Among those whose symptoms recurred, 14 patients underwent additional GKS, six MVD, four glycerol injection, and one patient a percutaneous radiofrequency rhizotomy. Twelve patients (9%) suffered the onset of new facial numbness post-GKS. Changes on MR images post-GKS were noted in nine patients (7%). On univariate analysis, right-sided neuralgia (p = 0.0002) and a previous neurectomy (p = 0.04) correlated with a pain-free outcome; on multivariate analysis, both right-sided neuralgia (p = 0.032) and patient age (p = 0.05) were statistically significant. New onset of facial numbness following GKS correlated with undergoing more than one GKS (p = 0.002). Conclusions. At the last follow up, GKS effected pain relief in 44% of patients. Some degree of pain improvement at 3 years post-GKS was noted in 70% of patients with TN. Although less effective than MVD, GKS remains a reasonable treatment option for those unwilling or unable to undergo more invasive surgical approaches and offers a low risk of side effects.

Object. The authors conducted a study to evaluate the safety and efficacy of gamma knife surgery (GKS) for the treatment of brain metastases from lung cancer. Methods. Between February 1993 and May 2003 191 patients underwent treatment for 424 brain metastases from non—small (171 cases) and small cell lung carcinoma (20 cases). Imaging and clinical status were monitored every 3 months following the treatment. Kaplan-Meier survival curves, Cox proportional hazards regression for risk factor analysis, and nonparametric methods for evaluating tumor response were used. There was no difference in median survival following combined whole-brain radiation therapy (WBRT) and gamma knife surgery (14 months) and GKS alone (15 months). There was also no difference between the median survival rates for either tumor type. In the multivariate analysis, age less than 65 years, Karnofsky Performance Scale score greater than 70, normal neurological status, multiple GKS treatments, and pre-GKS craniotomy were related to longer survival. Tumor control rates varied according to the volume of the metastases and were as follows: 84.4% (< 0.5 cm3), 94% (0.5–2 cm3), 89.1% (2–4 cm3), 93.4% (4–8 cm3), 85.7% (8–14 cm3), and 87.5% (> 14 cm3). Four lesions required post-GKS craniotomy due to swelling or rapid tumor progression. The rate of tumor shrinkage was higher when a volume was 2 cm3, lower in cystic lesions, lower in tumors with previous WBRT, and lower for margin doses less than 14 Gy. Conclusions. The risk—benefit ratio of GKS in this series was satisfactory. There was no difference in response rates of the two tumor types, and WBRT did not improve the duration of survival.

Object. The authors present data concerning the development of cysts following gamma knife surgery (GKS) in 1203 consecutive patients with arteriovenous malformations (AVMs) treated by the senior author (L.S.). The cyst was defined as a fluid-filled cavity at the site of a treated AVM. Cases involving regions corresponding to previous hematoma cavities were excluded. The incidence of cyst formation was assessed using magnetic resonance imaging studies performed in 196 cases with more than 10 years of follow up, in 332 cases with 5 to 10 years of follow up, and in 675 cases with less than 5 years of follow up. One hundred five cases were lost to follow-up study. The Cox regression method was used to analyze the factors related to cyst formation. Methods. The incidence of cyst formation in the entire patient population was 1.6 and 3.6% in those undergoing follow-up examination for more than 5 years. Ten of 20 cysts developed between 10 to 23 years, nine between 5 to 10 years, and one in less than 5 years following the treatment. Cyst fluid aspiration, cystoperitoneal shunt placement, or craniotomy were used in three symptomatic cases. Analysis of age, sex, and treatment parameters yielded no significant relationship with cyst formation; however, radiation-induced tissue change following GKS (p = 0.027) and prior embolization (p = 0.011) were related to cyst formation. Conclusions. Overall, the incidence of cyst formation in patients who underwent GKS for AVM was 1.6%. The development of the cyst was related to the duration of the follow-up period. When cysts are symptomatic, surgical intervention should be performed.

The state of the art of vestibular schwannoma management is reviewed with discussion of pertinent literature to bring out the current results and controversies in this field. Microsurgery results from four major series are discussed along with data from those using gamma knife or linear accelerators to treat these tumors.

Object. The goal of this study was to evaluate the results of gamma surgery in nine patients treated for vein of Galen malformations (VGMs).Methods. A consecutive series of nine VGMs in eight children aged 4 to 14 years and in one adult were treated with gamma surgery. Six of the patients were male, including the adult, and three were female. Among these patients there were three Yaşargil Type I, one Type II, two Type III, and three Type IV malformations. Previous embolization had failed in four cases. Three VGMs were treated with gamma surgery twice. An additional patient with a Type III VGM underwent stereotactic angiography in preparation for gamma surgery but was judged to be suitable for direct embolization.Follow-up angiograms were obtained in eight of the VGMs treated. Four no longer filled; one has probably been obliterated, but this cannot be confirmed because the patient refused to undergo final angiography; one patient has residual fistulas not included in the initial treatment field, which were retreated recently; and two other patients have marked reduction of flow through their VGMs.Conclusions. Gamma surgery is a viable option in the treatment of VGMs in clinically stable patients. Combined endovascular therapy and gamma surgery is of benefit in complex malformations.

Object. The goal of this study was to evaluate the effectiveness and limitations of gamma surgery (GS) in the treatment of renal cell carcinoma that has metastasized to the brain.Methods. The authors performed a retrospective analysis of a consecutive series of 21 patients with 37 metastatic brain deposits from renal cell carcinoma who were treated with GS at the University of Virginia from 1990 to 1999.Clinical data were available in all patients. No patient died of progression of intracranial disease or deteriorated neurologically following GS. Eight patients clinically improved. Follow-up imaging studies were available for 23 tumors in 12 patients. Nine patients did not undergo follow-up imaging. One patient lived 17 months and succumbed to systemic disease; no brain imaging was performed in this case. Another patient refused further imaging and lived 7 months. Seven patients lived up to 4 months after the procedure; however, their physicians did not require these patients to undergo follow-up imaging examinations because of their general conditions—all had systemic progression of disease. Of the 23 tumors that were observed posttreatment, one remained unchanged in volume, 16 decreased in volume, and six disappeared. No tumor progressed at any time, and there were no radiation-induced changes on follow-up imaging an average of 21 months after GS (range 3–63 months).Conclusions. Gamma surgery provides an alternative to surgical resection of metastatic brain deposits from renal cell carcinoma. Neurological side effects were seen in only one case; freedom from progression of disease was achieved in all cases.

To estimate the annual risk for the first hemorrhage, survival and life table statistics were used to analyze data from 2262 patients with cerebral arteriovenous malformations (AVM). We found that the risk for hemorrhage increases with increasing age. A validity test revealed, however, that life table statistics used on the total patient material underestimated the annual risk for hemorrhage, especially for patients 20-50 years of age. A method based on the fact that the distribution of the time at risk until the initial hemorrhage (= age at first rupture) reflects the risk for hemorrhage in untreated AVM was therefore also employed. The analysis yielded three conclusions: 1) the annual risk of hemorrhage increases with age; 2) small AVM are less prone to rupture; and 3) the risk of hemorrhage is higher in women during their fertile years as compared to males in the same age group. The risk related to age, AVM size and location assessed by survival statistics in the subgroup of patients with a known date for the initial hemorrhage gave similar results.

To define the factors of importance for the obliteration of cerebral arteriovenous malformations (AVMs), thus making a prediction of the probability for obliteration possible.In 945 AVMs of a series of 1319 patients treated with the gamma knife during 1970 to 1990, the relationship between patient, AVMs, and treatment parameters on the one hand and the obliteration of the nidus on the other was analyzed.The obliteration rate increased both with increased minimum (lowest periphery) and average dose and decreased with increased AVM volume. The minimum dose to the AVMs was the decisive dose factor for the treatment result. The higher the minimum dose, the higher the chance for total obliteration. The curve illustrating this relation increased logarithmically to a value of 87%. A higher average dose shortened the latency to AVM obliteration. For the obliterated cases, the larger the malformation, the lower the minimum dose used. This prompted us to relate the obliteration rate to the product minimum dose (AVM volume)1/3 (K index). The obliteration rate increased linearly with the K index up to a value of approximately 27, and for higher K values, the obliteration rate had a constant value of approximately 80%. For the group of 273 cases treated with a minimum dose of at least 25 Gy, the obliteration rate at the study end point (defined as 2-yr latency) was 80% (95% confidence interval = 75-85%). If obliterations that occurred beyond the end point are included, the obliteration rate increased to 85% (81-89%).The probability of obliteration of AVMs after gamma knife surgery is related both to the lowest dose to the AVMs and the AVM volume, and it can be predicted using the K index.

The authors commemorate the life and career of Dr. Ladislau Steiner, one of the world's most highly regarded neurosurgeons, from Stockholm and Charlottesville, Virginia, who has died at age 92. They review the events of Dr. Steiner's early life, including his early training in his native Romania, his escape with his family from East Berlin, and his postgraduate training in neurosurgery at the Karolinska Institute in Stockholm. Dr. Steiner's work in the development of microsurgery and his collaboration with Lars Leksell in the development of Gamma Knife radiosurgery are described. After his retirement from Karolinska, Dr. Steiner had a second career as head of the Lars Leksell Gamma Knife Center at the University of Virginia in Charlottesville. The authors recall their own long association with Dr. Steiner and celebrate his contributions to the field of neurosurgery.

Stereotactic devices for experimental Gamma Knife irradiation and magnetic resonance imaging (MRI) have recently been developed for experimental studies using rats [6,7]. The present study examined the accuracy of these devices using the following two approaches. In the first approach, Gamma Knife irradiation was performed using the stereotactic device with targets based on a standard stereotactic atlas. Gadolinium-enhanced T1-weighted magnetic resonance imaging was performed using the MRI stereotactic device. Animals were then sacrificed after Evans blue injection, and the rat brain was sliced using an attachment to the stereotactic device. The center coordinates of the gadolinium-enhanced area from the MRI and Evans blue-stained area from the tissue sections were obtained using a computer-assisted image analysis system. These coordinates were compared with the target coordinates planned from the stereotactic atlas. In the second approach, a thermoluminescence dosimeter was implanted in the rat brain. Stereotactic MRI was performed using the stereotactic MRI device, and the coordinates of the implant were obtained. Gamma Knife irradiation was then performed at this target using the stereotactic device. The absorbed dose was measured and compared with the planning dose. These experiments demonstrated a spatial error of 0.6 mm (standard error +/- 0.07) between Gamma Knife irradiation based on a comparison of the atlas coordinates and the lesion, and a spatial error of 1.0 mm (standard error +/- 0.13) based on a comparison of the stereotactic MR images and the lesion. Gamma Knife irradiation based on MR images using the stereotactic device demonstrated a maximum error of 10% in absorbed dose at the target center. Together, the stereotactic devices for Gamma Knife irradiation and magnetic resonance imaging provide useful tools for Gamma Knife research in an animal model.

Three patients with pituitary adenomas (ACTH-secreting, non-secretory, and multi-secretory) with unfavorable course, in spite of repeated microsurgery, drug therapy, as well as radiotherapy and radiosurgery, are presented. Each case was re-evaluated for possible flaws in management. Two of the invasive tumors continued to grow, in spite of correct management. The third patient with a pituitary adenoma underwent microsurgical resection, and later following a false positive finding of recurrence, received radiotherapy and underwent radiosurgery. The lesion actually was chronic inflammatory tissue.

A stereotactic device (SDM) was developed for performing consistent magnetic resonance imaging (MRI) of the rat brain. The SDM was developed by adapting a radiofrequency transmit/receive head coil of 4.4 cm inner diameter (quadrature birdcage head coil), and utilizing partial acrylic construction for the positioning elements. The small head coil provides improved resolution and accuracy of the image, while the stereotactic holder permits repeatable and accurate imaging of identified brain structures. This system provides several advantages over existing experimental MRI devices. The SDM ensures that the head is always placed in the center of the coil in a uniform fashion. Standardized positioning of the skull optimizes image quality and provides a consistent orientation of the brain. In addition, a widely-utilized coordinate system described by Paxinos and Watson can be employed to assist in the identification of structures and to facilitate surgical planning. The SDM is compatible with a recently-developed stereotactic device for radiosurgery with the Gamma Knife, thus permitting the planning and performance of experimental radiosurgery using the same coordinate system. The SDM also provides the ability to perform MRI and radiosurgery at different times, thus avoiding the need for prolonged anesthesia during an experimental study. Finally, the SDM allows repeated MRI of the same, identifiable positions in the brain during longitudinal experimental studies. The utility of this device is demonstrated here by examining the time course of cerebral damage that evolved within a radiosurgical focus after gamma irradiation.

Computed tomographic (CT), magnetic resonance (MR), MR angiographic and angiographic images, obtained after complete nidus obliteration had been angiographically confirmed, were reviewed in 9 patients who had undergone Gamma Knife treatment for cerebral arteriovenous malformations (AVMs). The period between angiographic confirmation of nidus obliteration and the most recent examinations was 12-84 months (mean 29 months). The patients ranged in age from 9 to 54 years (mean 22 years). There were 6 females and 3 males. In 8 patients, the obliterated nidus was shown on CT to be isodense. Calcification was identified in 3 patients, 1 of whom had not shown calcification on CT before treatment. Contrast enhancement of the nidus was seen in 6 patients, in 5 of whom a significant time-related decrease in contrast enhancement was observed following nidus obliteration. In 6 patients, T1-weighted MR imaging showed a hypointense nidus in 4 cases, both hypo- and isointense in 1 and isointense in 1. T2-weighted imaging showed a more varied nidus intensity than was seen on T1-weighted imaging. No flow signal void was demonstrated in any of these cases. After gadolinium administration, the nidus was enhanced in all cases, markedly in 4 and moderately in 2. In 5 of the 6 cases a time-related decrease in gadolinium enhancement was observed following nidus obliteration. This change was, however, less significant than that observed on contrast-enhanced CT. Angiography and/or MR angiography showed no vascular abnormalities in 7 patients. These results show that radiosurgery-induced changes in a nidus may continue for several years after angiography has shown complete AVM obliteration. These late changes can be considered to involve further obliteration of the remaining or recanalizing vessels, reflecting an ongoing process from coagulation necrosis to liquefaction necrosis.

Purpose: To investigate the temporal sequence of post radiosurgery magnetic resonance imaging changes in cerebral arteriovenous malformations. Methods and Materials: Eighteen patients were regularly followed up after gamma knife surgery. The follow-up intervals ranged from one day to 44 months. High signal lesion in or around arteriovenous malformations on T2-weighted magnetic resonance images corresponding to the treatment volume and developing after radiosurgery were defined as the adverse reaction of the irradiation. This high signal and the regression of arteriovenous malformations nidus after radiosurgery were evaluated. Results: Adverse reaction of irradiation was observed in nine cases. Seven of them were symptomatic. The reactions presented as focal high signal in three cases and focal high signal with extension along the neural tracts in six cases. The reactions were seen either immediately after treatment (one case), between 3 and 14 months (seven cases), and 40 months after treatment (one case). The regression of the adverse reaction was observed to start 5 ±3 months after its appearance. Regression of the arteriovenous malformations' nidus was found in 16 cases. In two cases the AVMs became invisible on magnetic resonance images but the angiogram still demonstrated abnormal shunts. In another one case with angiogram showing total obliteration, the nidus was erroneously interpreted as incomplete obliteration on magnetic resonance images. Conclusion: It is concluded that magnetic resonance imaging is a sensitive in vivo method for detecting cerebral radiation injury. Magnetic resonance imaging offers a method for evaluating the regression of arteriovenous malformations' nidus, but the diagnosis of complete obliteration of the nidus after radiosurgery still relies on the angiogram.

Fifteen patients were treated in the Gamma Knife Unit and followed for 18 months or longer. Four patients had Cushing's disease, 4 had acromegaly, 3 had Nelson's syndrome and 3 had prolactinomas. One patient had no endocrinopathy. One of the patients with acromegaly and 2 of those with prolactinomas had been operated prior to Gamma Knife treatment. Radiological tumor localization was not an insuperable problem in this series. The effect of Gamma Knife treatment on the anterior pituitary neoplasia, as such, was consistently successful. All the tumors which received 10 Gy or more to the edge showed either a reduction in volume or at least cessation of growth. On the other hand, the effect of the treatment was less consistent in respect to the endocrinopathies. These results are discussed in respect of dose and tumor size. It is suggested that the role of the Gamma Knife in the treatment of pituitary adenomas requires further clarification, based on prospective studies.

OBJECTIVE: The causes of failure after an initial Gamma procedure were studied, along with imaging and clinical outcomes, in a series of 140 patients with cerebral arteriovenous malformations (AVMs) treated with repeat Gamma Knife surgery (GKS). METHODS: Causes of initial treatment failure included inaccurate nidus definition in 14 patients, failure to fill part of the nidus as a result of hemodynamic factors in 16, recanalization of embolized AVM compartments in 6, and suboptimal dose (< 20 Gy) in 23. Nineteen patients had repeat GKS for subtotal obliteration of AVMs. In 62 patients, the AVM failed to obliterate despite correct target definition and adequate dose. At the time of retreatment, the nidus volume ranged from 0.1 to 6.9 cm 3 (mean, 1.4 cm 3 ), and the mean prescription dose was 20.3 Gy. RESULTS: Repeat GKS yielded a total angiographic obliteration in 77 patients (55%) and subtotal obliteration in 9 (6.4%). In 38 patients (27.1 %), the AVMs remained patent, and in 16 patients (11.4%), no flow voids were observed on magnetic resonance imaging. Clinically, 126 patients improved or remained stable, and 14 experienced deterioration (8 resulting from a rebleed, 2 caused by persistent arteriovenous shunting, and 4 related to radiation-induced changes). CONCLUSION: By using repeat GKS, we achieved a 55% angiographic cure rate. Although radiation-induced changes as visualized on magnetic resonance imaging occurred in 48 patients (39%), only 4 patients (3.6%) developed permanent neurological deficits. These findings may be useful in deciding the management of AVMs in whom total obliteration after initial GKS was not achieved.

Gamma Knife surgery (GKS) is a common treatment for recurrent or residual pituitary adenomas. This study evaluates a large cohort of patients with a pituitary adenoma to characterize factors related to endocrine remission, control of tumor growth, and development of pituitary deficiency.A total of 418 patients who underwent GKS with a minimum follow-up of 6 months (median 31 months) and for whom there was complete follow-up were evaluated. Statistical analysis was performed to evaluate for significant factors (p0.05) related to treatment outcomes.In patients with a secretory pituitary adenoma, the median time to endocrine remission was 48.9 months. The tumor margin radiation dose was inversely correlated with time to endocrine remission. Smaller adenoma volume correlated with improved endocrine remission in those with secretory adenomas. Cessation of pituitary suppressive medications at the time of GKS had a trend toward statistical significance in regard to influencing endocrine remission. In 90.3% of patients there was tumor control. A higher margin radiation dose significantly affected control of adenoma growth. New onset of a pituitary hormone deficiency following GKS was seen in 24.4% of patients. Treatment with pituitary hormone suppressive medication at the time of GKS, a prior craniotomy, and larger adenoma volume at the time of radiosurgery were significantly related to loss of pituitary function.Smaller adenoma volume improves the probability of endocrine remission and lowers the risk of new pituitary hormone deficiency with GKS. A higher margin dose offers a greater chance of endocrine remission and control of tumor growth.

Detailed follow-up results for 25 patients treated for cerebral arteriovenous malformation (AVM) with a gamma unit are presented. Complete nidus obliteration was angiographically confirmed in 16 (73%) of 22 cases receiving full-dose irradiation. There were no radiation- or AVM-related mortalities. However, we did experience one case of radiation-related morbidity and one of angiographyrelated mortality, the autopsy findings of which are discussed. Computed tomography scan and magnetic resonance imaging follow-up studies of radiosurgically treated AVMs indicated that increased enhancement of the nidus after contrast or gadolinium administration could persist even after obliteration of the AVM was angiographically confirmed.

Objective The safety, efficacy, and morbidity of radiosurgery (RS) must be established before it can be offered as an alternative to open surgery for unilateral mesial temporal lobe epilepsy. We report the 3-year outcomes of a multicenter, prospective pilot study of RS. Methods RS was randomized to 20 or 24Gy targeting the amygdala, hippocampus, and parahippocampal gyrus. Seizure diaries evaluated the final seizure remission between months 24 and 36. Verbal memory was evaluated at baseline and 24m with the Wechsler Memory Scale–Revised (WMS-R) and California Verbal Learning Test (CVLT). Patients were classified as having “significant improvement,” “no change,” and “significant impairment” based on relative change indices. Results Thirteen high-dose and 17 low-dose patients were treated. Both groups showed significant reductions in seizures by 1 year after treatment. At the 36-month follow-up evaluation, 67% of patients were free of seizures for the prior 12 months (high dose: 10/13, 76.9%; low dose: 10/17, 58.8%). Use of steroids, headaches, and visual field defects did not differ by dose or seizure remission. The prevalence of verbal memory impairment was 15% (4/26 patients); none declined on more than one measure. The prevalence of significant verbal memory improvements was 12% (3/26). Interpretation RS for unilateral mesial temporal lobe epilepsy offers seizure remission rates comparable with those reported previously for open surgery. There were no major safety concerns with high-dose RS compared with low-dose RS. Additional research is required to determine whether RS may be a treatment option for some patients with mesial temporal lobe epilepsy. Ann Neurol 2009

This study evaluates the safety and efficacy of gamma knife radiosurgery (GKRS) in patients with a growth hormone-secreting adenoma.A retrospective review of data collected from a prospective database of GKRS patients between January 1988 and September 2006 was performed in patients with acromegaly. Successful endocrine outcome was defined as normalization of the insulin-like growth factor level. Tumor volume was also assessed. At least 18 months of follow-up was available in 95 patients who received radiosurgery during the study period. Mean endocrine follow-up was 57 months (range, 18-168 mo).Normal insulin-like growth factor levels were achieved in 50 patients (53%) at an average time of 29.8 months after radiosurgery (median, 23.5 mo). A decrease in tumor volume control was achieved in 83 (92%) of 90 patients. Five patients (6%) had no change in tumor volume, and two patients (2%) had an increase in tumor volume. New endocrine deficiencies developed in 32 patients (34%). Four patients developed new-onset partial visual acuity deficits; three of these patients had received previous conventional fractionated radiation therapy.GKRS is a complementary treatment for recurrent or residual growth hormone-secreting pituitary adenomas. Although infrequent, tumor growth, new-onset pituitary hormone deficiency, recurrence, and neurological dysfunction require careful clinical, radiological, and endocrinological follow-up.

Object Focal tumors, a distinct subgroup of which is composed of brainstem gliomas, may have an indolent clinical course. In the past, their management involved monitoring of open-ended imaging studies and shunt placement if cerebrospinal fluid diversion was required. Nonetheless, their treatment remains a significant challenge for neurosurgeons. Gamma Knife surgery (GKS) has recently been tried as an alternative to surgical extirpation. In the present study the authors assess clinical and imaging results in 20 patients who harbored focal brainstem gliomas treated with GKS between 1990 and 2001. Methods There were 10 male and 10 female patients with a mean age of 19.1 years. Sixteen tumors were located in the midbrain, three in the pons, and one in the medulla oblongata. The mean tumor volume at the time of GKS was 2.5 cm3. In 10 cases a tumor specimen was obtained either by open surgery or stereotactic biopsy, securing the diagnosis of pilocytic astrocytoma in five patients and nonpilocytic astrocytoma in five others. In the remaining 10 cases, the diagnosis was based on clinical and neuroimaging findings. The prescription Gamma Knife dose varied between 10 and 18 Gy, except in three patients who were receiving a boost to a site in which external-beam radiation was previously delivered. An average of four isocenters were utilized per GKS. Patients were followed up for a mean of 78.0 months. The tumors disappeared in four patients and shrank in 12 patients. Of these patients, one experienced transitory extrapyramidal symptoms and fluctuating impairment of consciousness (from somnolence to coma) for 6 months. Another patient whose tumor disappeared 3 years following GKS died of stroke 8 years postoperatively. The rest of the patients either remained stable or improved clinically. Tumor progression occurred in four patients; of these four, one patient developed hydrocephalus requiring a ventriculoperitoneal shunt, two showed neurological deterioration, and one 4-year-old boy died of tumor progression. Conclusions Gamma Knife surgery may be an effective primary treatment or adjunct to open surgery for focal brainstem gliomas.

Object The authors review imaging and clinical outcomes in patients with metastatic brainstem tumors treated using Gamma Knife surgery (GKS). Methods Between March 1989 and March 2005, 53 patients (24 men and 29 women) with metastatic brainstem lesions underwent GKS. The metastatic deposits were located in the midbrain in eight patients, the pons in 42, and the medulla oblongata in three. Lung cancer was the most common primary malignancy, followed by breast cancer, melanoma, and renal cell carcinoma. The mean volume of the metastatic deposits at the time of treatment was 2.8 cm3 (range 0.05–21 cm3). The prescription doses varied from 9 to 25 Gy (mean 17.6 Gy). Imaging follow-up studies were not completed in 16 patients, because of the short-term survival in 11 and patient refusal in five. Of the remaining 37 patients, who underwent an imaging follow-up evaluation at a mean of 9.8 months (range 1–25 months), the tumors disappeared in seven, shrank in 22, remained unchanged in three, and grew in five. All but one of 18 patients with asymptomatic brainstem deposits remained free of symptoms. In 35 patients with symptomatic brainstem deposits, neurological symptoms improved in 21, remained stable in 11, and worsened in three. At the time of this study, 10 patients were alive, and their survival ranged from 3 to 52 months after treatment. Thirty-four patients died of extracranial disease, three of the progressing metastatic brainstem lesion, and six of additional progressing intracranial deposits in other parts of the brain. The overall median survival period was 11 months after GKS. In terms of survival, the absence of active extracranial disease was the only favorable prognostic factor. Neither previous whole-brain radiation therapy nor a single brainstem metastasis was statistically related to the duration of survival. Conclusions Compared with allowing a metastatic brainstem lesion to take its natural course, GKS prolongs survival. The risks associated with such treatment are low. The severity of systemic diseases largely determines the prognosis of metastases to the brainstem.