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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.

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.

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 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.

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.

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.

OBJECTIVE: Experience with gamma knife radiosurgery (GKRS) for prolactinomas is limited because of the efficacy of medical and surgical intervention. Patients who are refractory to medical and/or surgical therapy may be treated with GKRS. We characterize the efficacy of GKRS for medically and surgically refractory prolactinomas. METHODS: We reviewed our series of patients with prolactinomas who were treated with GKRS after failing medical and surgical intervention who had at least 1 year of follow-up. RESULTS: Twenty-three patients were included in analysis of endocrine outcomes (median and average follow-up of 55 and 58 mo, respectively) and 28 patients were included in analysis of imaging outcomes (median and average follow-up of 48 and 52 mo, respectively). Twenty-six percent of patients achieved a normal serum prolactin (remission) with an average time of 24.5 months. Remission was significantly associated with being off of a dopamine agonist at the time of GKRS and a tumor volume less than 3.0 cm3 (P < 0.05 for both). Long-term image-based volumetric control was achieved in 89% of patients. Complications included new pituitary hormone deficiencies in 28% of patients and cranial nerve palsy in two patients (7%). CONCLUSION: Clinical remission in 26% of treated patients is a modest result. However, because the GKRS treated tumors were refractory to other therapies and because complication rates were low, GKRS should be part of the armamentarium for treating refractory prolactinomas. Patients with tumors smaller than 3.0 cm3 and who are not receiving dopamine agonist at the time of treatment will likely benefit most.

OBJECT: Data regarding the long-term efficacy of Gamma knife surgery on a large series of patients with low-grade gliomas is lacking. We aimed to review the outcome of patients with low-grade gliomas undergoing Gamma knife surgery at the Lars Leksell Gamma Knife Center at the University of Virginia to clarify its role in the management of these lesions. METHODS: A retrospective review of 49 patients treated between 1989 and 2003 was conducted. The median follow up was 63 months. Gamma knife surgery was generally performed for tumors in eloquent brain, residual tumor post-surgery or for late progression after surgery. RESULTS: Median clinical progression free survival was 44 months and median radiological progression free survival was 37 months. Five-year radiological progression free survival was 37% while clinical progression free survival was 41%. Mortality due to tumor progression occurred in 7 patients (14%). Complete radiological remission was seen in 14 patients (29%). Complications due to Gamma surgery were seen in 4 patients (8%). Of these, two resolved without sequelae, one required surgery for neurological decline and associated radiation induced changes, and one patient suffered a permanent neurological deficit from treatment. CONCLUSION: Gamma knife radiosurgery is a safe treatment for low-grade gliomas and may be considered in patients with residual or recurrent disease.

Object. The aim of this study was to evaluate the usefulness and limitations of gamma surgery (GS) in the treatment of brain metastases from melanoma. Methods. Imaging and clinical outcomes in 45 patients treated for 92 brain metastases from melanoma between October 1989 and October 1999 were retrospectively analyzed. Follow-up imaging studies were available in 35 patients with 66 treated lesions. Twenty-four percent of the lesions disappeared, 35% shrank, 23% remained unchanged, and 18% increased in size. No undue radiation-induced changes were observed in the surrounding brain. Clinical data were available in all patients. No deaths or neurological morbidity related to GS was observed. The median survival time, calculated using the Kaplan—Meier method, was 10.4 months from the time of GS. In both univariate and multivariate Cox regression analyses, a single brain lesion and lack of visceral metastases were statistically predictive of a better prognosis. Six of eight patients with solitary metastasis (that is, a single brain metastasis with no primary visceral tumor) were still alive at the close of the study, none of them with disease progression, with a follow-up period ranging between 14 and 82 months. Sixteen patients in this series received adjunctive whole-brain radiation therapy, which had no impact on their survival time or local and distant control of the brain disease. Conclusions. Gamma surgery is effective in treating melanoma metastases in the brain. It appears that the radiobiology of a single high dose overcomes the radioresistance barrier, yielding better results than fractionated radiation.

OBJECTIVE Radiosurgery is used as a therapeutic modality for a wide range of cerebral disorders. It is important to understand the underlying causes of deleterious side effects that may accompany gamma-irradiation of brain tissue. In this study, structural alterations in rat cerebral vessels subjected to gamma knife irradiation in vivo were examined, for elucidation of their potential role in necrosis formation. METHODS A maximal center dose of 75 Gy was delivered to the rat parietal cortex with a 4-mm collimator, and changes occurring before necrosis formation were assessed 3.5 months after irradiation. Transmission electron microscopy, using horseradish peroxidase as a tracer, and scanning electron microscopy with vascular casting were performed. RESULTS The capillary network in the irradiated area exhibited thickening and vacuolation of the basement membrane. The capillary density in the irradiated area was lower and the average capillary diameter was larger, compared with the nonirradiated side. These results indicate that substantial changes in the neuropil do not occur 2 weeks before the time of definite necrosis formation, whereas changes in the basement membrane are prominent. CONCLUSION The necrotic response to intermediate doses of focused-beam irradiation appears after a considerable latency period and then progresses rapidly. This contrasts with previously reported responses to fractionated whole-brain irradiation, in which damage occurs slowly and gradually. Alterations in the microvascular basement membrane precede overt cellular changes in neuronal and vascular cells and provide an early index of cerebrovascular dysfunction in regions destined to undergo necrosis.

Object. The management of intractable epilepsy remains a challenge, despite advances in its surgical and nonsurgical treatment. The identification of low-risk, low-cost therapeutic strategies that lead to improved outcome is therefore an important ongoing goal of basic and clinical research. Single-dose focal ionizing beam radiation delivered at necrosis- inducing and subnecrotic levels was investigated for its effects on seizure activity by using an established model of chronic recurrent spontaneous limbic seizures in rats. Methods. A single 90-minute period of repetitive electrical stimulation (inducing stimulus) of the hippocampus in rats elicited a single episode of status epilepticus, followed by a 2- to 4-week seizure-free period. Spontaneous recurrent seizures developed subsequently and persisted for the duration of monitoring (2–10 months). Simultaneous computerized electroencephalography and video recording were used to monitor the animals. After the establishment of spontaneous recurrent seizures, bilateral radiation centered in the ventral hippocampal formation was administered with the Leksell gamma knife, aided by a stereotactic device custom made for small animals. A center dose of 10, 20, or 40 Gy was administered using a 4-mm collimator. Control animals were subjected to the same seizure-inducing stimulus but underwent a sham treatment instead of gamma irradiation. In a second experiment, the authors examined the effects of gamma irradiation on the proclivity of hippocampal neurons to display epileptiform discharges. Naive animals were irradiated with a single 40-Gy dose, as already described. Slices of the hippocampus were prepared from animals killed between 1 and 178 days postirradiation. Sensitivity to penicillin-induced epileptiform spiking was examined in vitro in slices prepared from control and irradiated rat brains. Conclusions. In the first experiment, single doses of 20 or 40 Gy (but not 10 Gy) reduced substantially, and in some cases eliminated, behaviorally and electrographically recognized seizures. Significant reductions in both the frequency and duration of spontaneous seizures were observed during a follow-up period of up to 10 months postradiation. Histological examination of the targeted region did not reveal signs of necrosis. These findings indicate that single-dose focal ionizing beam irradiation at subnecrotic dosages reduces or eliminates repetitive spontaneous seizures in a rat model of temporal lobe epilepsy. In the second experiment, synaptically driven neuronal firing was shown to be intact in hippocampal neurons subjected to 40-Gy doses. However, the susceptibility to penicillin-induced epileptiform activity was reduced in the brain slices of animals receiving 40-Gy doses, compared with those from control rats that were not irradiated. The results provide rational support for the utility of subnecrotic gamma irradiation as a therapeutic strategy for treating epilepsy. These findings also provide evidence that a functional increase in the seizure threshold of hippocampal neurons contributes to the anticonvulsant influence of subnecrotic gamma irradiation.

¶ A retrospective analysis of a consecutive series of 12 patients with 15 intracranial hemangiopericytomas treated at the University of Virginia using Gamma surgery is presented. Clinical and radiographic follow up of 3 to 56 months is available for 10 patients with 12 tumors. There was one tumor present at the time of initial Gamma surgery in each patient. Two new tumors occurred in patients previously treated. Nine of the tumors decreased in volume and three remained stable. Four of the nine tumors that shrank later progressed at an average of 22 months after treatment. Of the tumors that decreased in volume and have not progressed, the response has been for an average of 11 months. The follow-up for two tumors that remained unchanged was 10 and 34 months (average 22 months). A third tumor was unchanged at 42 months but the patient died of new disease adjacent to the treated area in the anterior skull base. There were no complications and the quality of life following the procedure was maintained or improved in every case. Gamma surgery is effective in palliating the patients by decreasing tumor volume and delaying recurrence.

Objective The goal was to report the treatment results after a second gamma knife treatment and to compare them with the results obtained after a first gamma knife treatment, as well as to investigate whether the models to predict the results after a first treatment are also applicable after gamma knife treatment of previously irradiated arteriovenous malformations. Methods The number of complications and the posttreatment hemorrhage rate were recorded for 112 patients in the study, and the number of obliterations was recorded for the 101 patients for whom conclusive angiograms were obtained. The results were compared with the expected results after a first gamma knife treatment. Results The observed number of obliterations was 62, which is not significantly different from the predicted number of 65. There were 14 observed and 5 predicted complications. When the risk from the preceding radiation treatment was added, the observed number of complications was similar to the predicted number. Six hemorrhages were observed after the second treatment. Of the 5 patients with unchanged arteriovenous malformation size after both the first and second treatments, 2 experienced hemorrhages after the second treatment, compared with none among the 81 patients for whom the malformation was obliterated or significantly decreased in size after the second treatment. Conclusions The obliteration rate after gamma knife surgery for previously irradiated arteriovenous malformations is similar to that after primary gamma knife treatment. The complication rate increases with the amount of radiation previously given. The incidence of posttreatment hemorrhages is lower in the latency period if the malformation is affected by the radiation.

✓ Eight patients, ranging in age from 9 to 18 years, were treated for arteriovenous malformations using gamma knife radiosurgery and were evaluated an average of 6 years after treatment to record potential effects of radiosurgery on cognitive and neuropsychological performance. Tests for general intelligence, nonverbal intelligence, memory and its components, and attention performance were administered to patients and compared with test results of age-matched siblings or first cousins. No statistically significant difference was found between the performance of patients and controls in any of the tests administered. Additionally, a specially designed questionnaire completed by the patients, their parents, and their teachers revealed that the patients' emotional and relational behavior was stable and unchanged after treatment. No correlation was found between the neurocognitive test performance and the lesion volumes irradiated, but the lesion site was found to contribute to the type of deficit recorded after treatment. The less invasive nature of the radiosurgical approach, combined with the brevity or absence of hospitalization, presumably contributed to the patients' successful physical, mental, and emotional recovery.

BACKGROUND Following radiosurgical treatment, the majority of patients with arteriovenous malformations (AVMs) are periodically examined by means of computed tomography (CT) and magnetic resonance imaging (MRI) to assess the attainment of nidus obliteration, as well as adverse radiation effects in the surrounding brain. However, few neuroimaging studies of the long-term results following complete obliteration, confirmed by angiography, have been published to date. METHODS CT, MRI, magnetic resonance (MR) angiographic and angiographic images, obtained after angiographic confirmation of complete nidus obliteration, were reviewed in 11 AVM patients treated with gamma knife radiosurgery. The period between angiographic confirmation of nidus obliteration and these most recent examinations was 12–84 months (mean, 29 months). RESULTS In ten patients who were assessed by CT, the obliterated nidus was shown to be isodense (eight cases) or a mixture of isodense and hypodense areas (two cases). A significant time-related decrease in contrast enhancement was observed within 1 to 2 postobliteration years (five/seven cases). Eight patients were evaluated by MRI. On T1-weighted imaging, the nidus was shown to be hypointense (six cases) or a mixture of hypointense and isointense areas (two cases). On T2-weighted imaging, nidus intensity varied more than that observed on T1-weighted imaging, and time-related intensity increases were observed (two/seven cases). No flow-signal void was demonstrated in any of these cases. In four of the seven cases, in which serial postobliteration follow-up MRI studies were conducted, significant gadolinium enhancement persisted 3 years or more after obliteration (maximum of 7 years). No vascular abnormalities were demonstrated in seven patients who were assessed by conventional angiography and/or MR angiography. CONCLUSIONS Radiosurgery-induced changes in a nidus may continue for several years after angiography has shown complete AVM obliteration.

The anterior cerebral artery of rats was irradiated at the level of the circle of Willis by Gamma Knife with a maximum dose of 25, 50, or 100 Gy. Occlusion of the anterior cerebral artery was observed in one rat which was followed for 20 months after irradiation of 100 Gy. Cerebral infarction was found at the midline-frontal region and the cingulate gyrus. Arterial wall thickening with fibrosis, splitting of the internal elastic membrane, luminal organized thrombus, and migration of smooth muscle cells into the thrombus were observed. In the anterior cerebral artery, thrombus formation seemed to occur after the endothelial injury and this may play a prominent role for occlusion. In small arteries, various changes were observed in the irradiated tissue. These included fibrosis and thrombus, thickened smooth muscle layer, lymphocytic infiltration, and thickening of vessel wall with fibrosis and fibrinous thrombosis with leakage of fibrin into the surrounding tissue after different doses of radiation and at different observation times. These changes were comparable to the ordinary vascular response to injury including healing vasculitis and arteriosclerosis.

We present our results of Gamma Knife surgery for craniopharyngioma in nine patients. The current status of surgery, radiation therapy, intracavitary instillation of radionucleides and Gamma Knife surgery in the management of craniopharyngiomas is discussed.

✓ Radiosurgical treatment with the gamma knife for venous angiomas was used as an alternative to microsurgical removal in order to avoid abrupt cessation of venous drainage, which may be shared by the venous angioma and important parts of the brain. Thirteen cases of venous angioma were treated between 1977 and 1991. In two cases cavernous angiomas were also present and in one case a distant arteriovenous malformation (AVM) was also found. In two cases the angioma shared the venous drainage with an adjoining AVM; this is the first description of such pathology. For venous angiomas irradiation was prescribed to cover at least the convergence of the medullary veins. For AVM's close to a venous angioma the treatment was exclusively prescribed to the AVM nidus. After treatment, complete obliteration of the venous angioma was observed in one case, partial obliteration was observed in three cases, and five venous angiomas were unaffected by the treatment. Undue effects of radiation occurred in four cases: one focal edema and three radionecroses. Extirpation of the radionecrotic tissue 6 months after radiosurgery was necessary in one case. In the other three cases, the venous angioma was observed to be completely or partially obliterated, or unaffected by the treatment (one case each). In two cases of combined AVM and venous angioma, complete obliteration of the treatment AVM nidus was obtained. It is concluded that radiosurgery for venous angioma, although conceptually attractive, still does not fulfill the rigid criteria of minimal risk which must be set for the treatment of a lesion with a benign natural history.

Radiosurgery is used with increasing frequency, not only for the treatment of cerebral arteriovenous malformations (AVMs), but also for the treatment of other well-defined lesions including acoustic neuromas, meningiomas, pituitary adenomas as well as solitary metastases. Although investigators have addressed dosimetric aspects of stereotactic radiosurgery in terms of target volume, little if any attention has been focused on the absorbed doses received at extracranial sites. Therefore, absorbed doses to the eye, thyroid, sternum and gonads were measured in 111 patients (100 adults and 11 children) using thermoluminescent dosimetry (TLDs). For the 100 adults, the average maximum target absorbed dose was 35 +/- 8 Gy. The measured absorbed dose in selected organs of adults from Gamma Knife radiosurgery using one or more isocenters was 9 +/- 8 cGy for the eye, 15 +/- 7 cGy for the thyroid, 20 +/- 10 cGy for the sternum and 3 +/- 2 cGy for the gonads. The absorbed doses received by the children (13 years and younger) was similar with the exception of a marked increase in gonadal dose. The use of multiple isocenters is associated with higher absorbed doses to extracranial sites.

We describe our experience with stereotactic microsurgical resection of 27 lesions using the Leksell frame in 23 patients; 7 had cerebral metastases, 6 had gliomas, 6 had vascular malformations, 3 had meningiomas and 1 had radiation necrosis. Gross total removal of the lesion was accomplished in every case. All lesions were between 1.0 and 3.5 cm in greatest diameter and located either deep within the cerebral (n = 7) or superficially in areas of functional cortex (n = 20). There was no operative mortality and only minimal morbidity. Average length of operating time including frame application, imaging and resection was 4.4 h and most patients were discharged on the second postoperative day. The indications, advantages and limitations of stereotactic craniotomy are discussed and technical modifications that extend the usefulness and safety of this technique are described.

Long-term follow-up results of nine children treated for cerebral arteriovenous malformation with a gamma unit are presented. Complete nidus obliteration was angio-graphically confirmed in six cases and significant decreases in arteriovenous malformation size were observed in the other three. There were no radiation-related deteriorations in physical or mental development. In seven patients who underwent endocrinological examination more than 3 years after irradiation, five were normal and the other two showed only low serum adrenocorticotropic hormone levels, which, however, did not necessitate replacement therapy. Neurodiagnostic imaging follow-up studies revealed no radiation-induced lesions in any of the nine cases.

✓ The clinical outcomes are described for 247 consecutive cases of arteriovenous malformation (AVM) treated with the gamma knife between April, 1970, and December 31, 1983. Headache resolved in 65 (66.3%) of the 98 patients presenting with this symptom and improved in an additional nine (9.2%). Of 59 patients admitted with seizures, 11 (18.6%) became seizure-free without anticonvulsant medication and an additional 30 patients (50.8%) became seizure-free with anticonvulsant medication. Pre-existing neurological deficits improved or totally disappeared following radiosurgery in 56.7% of affected cases. This improvement presumably occurred within the frame of the natural history. The protective effect of the ionizing beams against hemorrhage in incompletely obliterated AVM's is analyzed. To assess the rate of rebleeding, probability estimates were calculated using both the person-year method and the Kaplan-Meier life table. With the person-year method the actual rebleed rate is not too different from the values observed in the natural history of the disease (2% to 3%/yr). Analysis by Kaplan-Meier life-table estimates demonstrated a risk of nearly 3.7%/yr until 60 months after radiosurgery. Five years following treatment, the life table ends in a plateau which could be interpreted as an indication of decrease in the risk of hemorrhage. However, long flat regions at the right end of the life table do not imply that the real risk of rebleeding is negligible unless a large number of patients have been followed well into or beyond the flat region.

Fifty (50) selected patients with arteriovenous malformation (AVM) with and without subarachnoid haemorrhage (SAH) were investigated, in respect of occurrence and course of the vasospasm. The diameters of the carotid siphon and its main branches were measured and plotted against the time elapsing between the haemorrhage and the angiographic study. Patients without SAH were used as a reference group. The results suggest intracranial arterial spasm to occur between the third and eleventh day after the onset of SAH. Patients with intracerebral haematoma may show vasospasm from the first day onwards. It seems that the radiologically demonstrated spasm in AVM had no impact on the clinical outcome in this series.

✓ Four-vessel angiography was repeated in 56 patients with confirmed subarachnoid hemorrhage in whom the initial investigation was negative. Only one aneurysm was demonstrated. The results suggest that, with good technique, careful observation, and a complete four-vessel cerebral angiography, a false negative rate of less than 2% can be achieved. It is suggested that to repeat pan-angiography is seldom justified unless further bleeding episodes occur.

Thalamotomy aiming at the CM-Pf complex and using stereotactic gamma irradiation has been performed in a series of 52 patients with severe pain due to malignancy. Lesions were produced either contra- or ipsilaterally to the side of the pain as well as bilaterally. Eight patients experienced good pain relief, 18 had moderate relief, and in 24 the operation did not significantly influence the pain. A second operation following recurrence of pain was rarely of value. There was a tendency towards more efficient relief of pain located in the face or in the arm and shoulder than of pain in the lower part of the body. Although contralateral lesions seem to be most effective, ipsilateral operations may also give some relief. The best results were obtained when the lesions were placed close to the wall of the third ventricle and at the level of the posterior commissure. Postmortem examination of 21 brains disclosed that the mean error in the placing of the lesions was about 1 mm. It is concluded that medial thalamotomy may be tried as a last resort in the treatment of cancer pain in selected patients with a short life expectancy.

The brain tissue reaction to a recently devised titanium haemoclip and to the conventional silver and tantalum clips were investigated in rabbit brain. Titanium, silver, and tantalum wires 5 X 0.5 X 0.5 mm in size were implanted into the white matter of the brain. After one and six months the brain specimens were sectioned, stained with haematoxylin eosin and with phosphotungstic acid Haematoxylin, and were studied by light microscopy. The examination revealed neither tissue reaction nor pigmentation in the case of titanium implant, while there was pigmentation surrounding the tantalum, and there was pigmentation as well as reactive gliosis around the silver wires.

A technique for stereotactic radiation therapy of cerebral tumours and arteriovenous malformations using a linear accelerator (6 MV photons) is proposed. Treatment relies on a fixation system that permits a precise use of the coordinates estimated at stereotactic angiography or stereotactic computed tomography. The field of treatment can be exactly outlined in the CT images during repeat examinations, thus facilitating the recognition of changes induced by radiation. The system also allows the extent of the arteriovenous malformation, as seen at angiography, to be accurately traced in the CT sections thus enabling evaluation of possible radiation damage to surrounding brain structures. The precision of the method as well as its hypothetical merits and disadvantages are discussed. The number of patients treated is still small and the follow-up time is too short in the majority of cases to allow definite conclusions. Examples of preliminary results are given.

✓ The quality of survival of 150 patients with arteriovenous malformations of the brain is presented. The mean period of follow-up was over 15 years. The surgically operated and conservatively managed groups are compared, a comparison that in the long run appears to favor the operated cases. The results are discussed and indications for surgery summarized.