European consensus conference on unruptured brain AVMs treatment (Supported by EANS, ESMINT, EGKS, and SINCH).

In December of 2016, a Consensus Conference on unruptured AVM treatment, involving 24 members of the three European societies dealing with the treatment of cerebral AVMs (EANS, ESMINT, and EGKS) was held in Milan, Italy. The panel made the following statements and general recommendations: (1) Brain arteriovenous malformation (AVM) is a complex disease associated with potentially severe natural history; (2) The results of a randomized trial (ARUBA) cannot be applied equally for all unruptured brain arteriovenous malformation (uBAVM) and for all treatment modalities; (3) Considering the multiple treatment modalities available, patients with uBAVMs should be evaluated by an interdisciplinary neurovascular team consisting of neurosurgeons, neurointerventionalists, radiosurgeons, and neurologists experienced in the diagnosis and treatment of brain AVM; (4) Balancing the risk of hemorrhage and the associated restrictions of everyday activities related to untreated unruptured AVMs against the risk of treatment, there are sufficient indications to treat unruptured AVMs grade 1 and 2 (Spetzler-Martin); (5) There may be indications for treating patients with higher grades, based on a case-to-case consensus decision of the experienced team; (6) If treatment is indicated, the primary strategy should be defined by the multidisciplinary team prior to the beginning of the treatment and should aim at complete eradication of the uBAVM; (7) After having considered the pros and cons of a randomized trial vs. a registry, the panel proposed a prospective European Multidisciplinary Registry.

Stereotactic radiosurgery for trigeminal schwannomas.

PURPOSE: Traditionally trigeminal schwannomas (TS) have been treated microsurgically; however, this is often associated with significant morbidity, and complete excision remains a challenge. Stereotactic radiosurgery (SRS) offers a minimally invasive alternative in treating TS. We report on our cumulative experience of using SRS in the treatment of TS. MATERIALS AND METHODS: Seventy-four TS patients (four with NF2) were treated with SRS using the Leksell Gamma Knife. Mean age (±1 SD) at treatment was 47.1 (15.5) years with a mean interval between presentation and treatment of 30.9 months. Thirty (40.5%) patients had undergone previous surgery on average 47.3 months prior to SRS. The average target volume was 5.3 cm(3) (range 0.4-19.9 cm(3)) and was treated with a mean prescription dose of 16.4 (3.9) Gy to the tumour margin. RESULTS: Average follow-up was 48.2 months (range 6-168 months). Tumour size remained static in 58 (78.4%) patients and showed radiological evidence of shrinkage in 11 (14.9%). Tumour progression occurred in five (6.6%) patients on average 40 months after SRS (range 12-108). Progression-free survival (PFS) for all patients was 98.5% at 1 year, 92.7% at 5 years and 79.4% at 10 years. Log-rank analysis indicated a significantly worse outcome for NF2 patients (p = 0.001) who demonstrated a PFS of 100% at 1 year and 50% at 5 years. Seven patients developed adverse radiation effects whilst improvements in pre-treatment cranial nerve dysfunction were achieved in eight patients. CONCLUSIONS: SRS is an effective treatment option in patients with residual or newly diagnosed TS. In view of the results of this study we would advocate a more front-line role for the Gamma Knife in the treatment of this tumour group.

A historical analysis of single-stage γ knife radiosurgical treatment for large arteriovenous malformations: evolution and outcomes.

BACKGROUND: Large arteriovenous malformations (AVMs) remain challenging and difficult to treat, reflected by evolving strategies developed from simple radiosurgical plans, to encompass embolization and, recently, staged volume treatments. To establish a baseline for future practice, we reviewed our clinical experience. METHOD: The outcomes for 492 patients (564 treatments) with AVMs >10 cm(3) treated by single-stage radiosurgery were retrospectively analysed in terms of planning, previous embolization and size. RESULTS: Twenty-eight percent of the patients presented with haemorrhage at a median age of 29 years (range: 2-75). From 1986 to 1993 (157 patients) plans were simplistic, based on angiography using a median of 2 isocentres and a marginal dose of 23 Gy covering 45-70% of the AVM (median volume 15.7 cm(3)). From 1994 to 2000 (225 patients) plans became more sophisticated, a median of 5 isocentres was used, covering 64-95% of the AVM (14.6 cm(3)), with a marginal dose of 21 Gy. Since 2000, MRI has been used with angiography to plan for 182 patients. Median isocentres increased to 7 with similar coverage (62-94%) of the AVM (14.3 cm(3)) and marginal dose of 21 Gy. Twenty-seven percent, 30% and 52% of patients achieved obliteration at 4 years, respectively. The proportion of prior embolization increased from 9% to 44% during the study. Excluding the embolized patients, improvement in planning increased obliteration rates from 28% to 36% and finally 63%. Improving treatment plans did not significantly decrease the rate of persisting radiation-induced side effects (12-16.5%). Complication rate rose with increasing size. One hundred and twenty-three patients underwent a second radiosurgical treatment, with a 64% obliteration rate, and mild and rare complications (6%). CONCLUSIONS: Better visualization of the nidus with multimodality imaging improved obliteration rates without changing morbidity. Our results support the view that prior embolization can make interpretation of the nidus more difficult, reducing obliteration rate. It will be important to see how results of staged volume radiosurgery compare with this historical material.

Survival and complications following γ knife radiosurgery or enucleation for ocular melanoma: a 20-year experience.

BACKGROUND: We present our experience in treating ocular melanoma at the National Centre for Stereotactic Radiosurgery in Sheffield, UK over the last 20 years. METHOD: We analysed 170 patients treated with Gamma Knife radiosurgery, recorded the evolution of visual acuity and complication rates, and compared their survival with 620 patients treated with eye enucleation. Different peripheral doses (using the 50% therapeutic isodose) were employed: 50-70 Gy for 24 patients, 45 Gy for 71 patients, 35 Gy for 62 patients. FINDINGS: There was no significant difference in survival between the 35-Gy, 45-Gy and 50- to 70-Gy groups when compared between themselves (p = 0.168) and with the enucleation group (p = 0.454). The 5-year survival rates were: 64% for 35 Gy, 62.71% for 45 Gy, 63.6% for 50-70 Gy and 65.2% for enucleated patients. Clinical variables influencing survival for radiosurgery patients were tumour volume (p = 0.014) and location (median 66.4 vs 37.36 months for juxtapapillary vs peripheral tumours, respectively; p = 0.001), while age and gender did not prove significant. Regarding complications, using 35 Gy led to more than a 50% decrease, when compared with the 45-Gy dose, in the incidence of cataract, glaucoma and retinal detachment. Retinopathy, optic neuropathy and vitreous haemorrhage were not significantly influenced. Blindness decreased dramatically from 83.7% for 45 Gy to 31.4% for 35 Gy (p = 0.006), as well as post-radiosurgery enucleation: 23.9% for 45 Gy vs 6.45% for 35 Gy (p = 0.018). Visual acuity, recorded up to 5 years post-radiosurgery, was significantly better preserved for 35 Gy than for 45 Gy (p = 0.0003). CONCLUSIONS: Using 35 Gy led to a dramatic decrease in complications, vision loss and salvage enucleation, while not compromising patient survival.

Stereotactic radiosurgery for trigeminal neuralgia: outcomes and complications.

Stereotactic radiosurgery is one of a number of recognised treatments for the management of trigeminal neuralgia refractory to drug therapy. The reported success of stereotactic radiosurgery in managing patients with trigeminal neuralgia varies in different units from 22 to 75%. This paper reports the outcomes of patients with trigeminal neuralgia who were treated at the National Centre for Stereotactic Radiosurgery in Sheffield, UK. The study reports the outcome of 72 patients treated consecutively between October 2004 and May 2008. Data were collected prospectively by a postal questionnaire sent to patients at 6, 12 and 24 months after treatment. The median age was 65.6 years (39 males: 33 females). Fourteen patients had secondary trigeminal neuralgia (eight multiple sclerosis). Fifteen of the patients included in the study were receiving a second treatment (an initial treatment having improved their pain significantly for at least 6 months). All radiosurgical procedures were performed using a single 4 mm collimator isocenter covering the region of the dorsal root entry zone with a maximal radiation dose of 80 Gy. The percentage of patients defined as having an excellent outcome (pain free without medication) was 39% after 6 months, 36% after 12 months and 64% after 24 months. The percentage of patients who reported being very satisfied with treatment was 71% after 6 months, 57% after 12 months and 53% after 24 months. Half the patients with secondary trigeminal neuralgia were pain free without medication after treatment, and 60% of patients who underwent a second treatment were pain free. A new trigeminal sensory deficit was reported by 31% of patients after radiosurgical treatment.

Stereotactic radiosurgery for pineal tumours.

OBJECTIVES: Pineal tumours continue to present considerable clinical dilemmas and challenges. We were, therefore, interested to review our cumulative experience with a view to formulating a potential treatment strategy. METHODS: A retrospective analysis of all patients treated with Stereotactic radiosurgery (SRS) for pineal tumours in one centre between 1987 and 2009. Forty-four patients (66% male) were treated radiosurgically with a mean age(± 1 sd) of 33.6 (16.4) years. Eleven had biopsy-proven pineal parenchymal tumours (PPT), six astrocytomas, three ependymomas, two papillary epithelial tumours and two germ cell tumours. Twenty (45%) patients had no definitive histology despite attempted surgical biopsy in 11. Prior to radiosurgery, 17 had undergone craniotomy, 10 radiotherapy and four chemotherapy. Nine patients were referred for primary SRS. RESULTS: Fifty Gamma knife treatments were performed on 44 patients prescribing 18.1 (4.2) Gy with a treatment volume of 3.8 (3.8) cm( 3 ). Routine clinical and MRI assessments were reviewed to calculate control rates. Mean follow up was 62.5 (52.9) months. Five patients (two ependymomas and three PPT) died at 36.2 (36.7) months after initial radiosurgical treatment. Overall progression-free survival (PFS) results were 93% at 1 year, 77% at 5 years, 67% at 10 and 20 years. Log-rank analysis revealed that higher initial tumour grade (P = 0.04), previous radiotherapy (P = 0.002) and radiological evidence of necrosis (P = 0.03) were associated with worse outcomes. The 5-year PFS for patients who possessed these 'aggressive' features was 47.1% compared with 91% for those patients who did not have these features. No persistent complications were attributed to SRS. CONCLUSIONS: These results further demonstrate the increasingly significant role played by STRS in the treatment of pineal tumours. Based on our findings, we believe a re-examination of the role of more established therapies for this patient group may be warranted.

Operative intervention for delayed symptomatic radionecrotic masses developing following stereotactic radiosurgery for cerebral arteriovenous malformations--case analysis and literature review.

CASE REPORT: We report two cases of operative intervention that was beneficial in the treatment of delayed symptomatic radionecrotic masses that had developed following stereotactic radiosurgery (SRS) using the gamma knife (GK) for the treatment of cerebral arteriovenous malformations (AVM). DISCUSSION: Case 1 involved a small craniotomy for decompression of a large cerebral multiloculated cyst, which had become symptomatic 84 months following gamma knife treatment for a left frontal lobe AVM. Case 2 involved surgical excision of an occipital radionecrotic mass 72 months following GK treatment for an occipital AVM. This patient had suffered from longstanding symptomatic cerebral oedema, which on occasions had become life threatening. Case 2 is also the first report of a radionecrotic mass occurring post-SRS for an AVM, which conversely appeared to demonstrate increased uptake on single photon emission computed tomography (SPECT) scan. The first literature review of such delayed symptomatic radionecrotic lesions is presented. There appears to be a late onset of symptoms (average 55 months, range 12-111 months) associated with such radionecrosis. Drainage of such cysts or excision of the mass lesion appears to be consistently beneficial to the patients and appears to be uncomplicated. CONCLUSION: We recommend early surgical intervention for such delayed symptomatic radionecrotic masses that do not resolve following non-operative management. We also recommend caution in interpretation of SPECT scan results when attempting to differentiate radionecrosis from neoplasia.

Application of a Relative Visual Performance Model in a Virtual Reality Immersive System.

As part of an evaluation process of user experience realism in a Virtual Reality (VR) system, we focus in this paper on one of the core characteristics of vision: the relationship between contrast and luminance. The experiment aims at validating in VR reaction time predictions given by Rea and Ouellette's model. The subjects have to distinguish, as fast as they can, a target object from an uniform background. Our results did not match the predictions of the model. Our subjects showed higher performance in performing the task than expected. At low level of contrast, our subjects could easily perceive a target they should not have been able to see at all. This is explained by the size of the visual field surrounding the target: at low level of visibility, the larger the surrounding, the easier perception the is. We conclude that the Rea and Ouellette's model could be applied in VR if a specific visual field size factor was added.

Evaluation of Spatial Filtering Algorithms for Visual Interactions in CAVEs.

We present an approach to solving the problem of haptic and visual misalignment in CAVEs. The approach moves the collision box for the virtual screen's buttons to coincide with where the user perceives their virtual location. Different filtering strategies were used. We evaluated the algorithms with simulations and with real subjects.

Performance Evaluation of Passive Haptic Feedback for Tactile HMI Design in CAVEs.

This article presents a comparison of different haptic systems, which are designed to simulate flat Human Machine Interfaces (HMIs) like touchscreens in virtual environments (VEs) such as CAVEs, and their respective performance. We compare a tangible passive transparent slate to a classic tablet and a sensory substitution system. These systems were tested during a controlled experiment. The performance and impressions from 20 subjects were collected to understand more about the modalities in the given context. The results show that the preferences of the subjects are strongly related to the use-cases and needs. In terms of performance, passive haptics proved to be significantly useful, acting as a space reference and a real-time continuous calibration system, allowing subjects to have lower execution durations and relative errors. Sensory substitution induced perception drifts during the experiment, causing significant performance disparities, demonstrating the low robustness of perception when spatial cues are insufficiently available. Our findings offer a better understanding on the nature of perception drifts and the need of strong multisensory spatial markers for such use-cases in CAVEs. The importance of a relevant haptic modality specifically designed to match a precise use-case is also emphasized.

Repeat Radiosurgery Treatment After Cavernous Malformation Radiosurgery.

OBJECTIVE: Of cavernous malformations (CMs) treated with radiosurgery (RS), 5% bleed after 2-year initial latency period. This rate is similar to failure rate of RS for other pathologies, which often require repeat RS for favorable outcome. The aim of this pilot study was to define failure of CM RS and to assess safety of second RS. METHODS: Retrospective analysis was performed of 7 of 345 CMs retreated with RS; 6 CMs were deep-seated, and 1 was superficial. Median time between the 2 treatments was 8 years (range, 3-16 years), and median follow-up time after second RS was 3 years (range, 1-9 years). RESULTS: Following the 2-year latency period after RS, 6% of deep-seated and 5% of hemispheric CMs, and 6% of deep-seated and 2% of hemispheric lesions caused transient neurologic deficits without hemorrhage. A second treatment was indicated for rebleed in 5 cases and for recurrent transient neurologic deficits in 2 cases. Prescribed dose was 15 Gy (range, 12-20 Gy) at first treatment and 12 Gy (range, 12-18 Gy) at second treatment. Target volumes were 692 mm3 (range, 54-2400 mm3) and 935 mm3 (range, 150-1550 mm3) at first and second treatments, respectively, and treatment volumes were 811 mm3 (range, 79-2500 mm3) and 962 mm3 (range, 194-1750 mm3), respectively. Differences in treatment parameters were not significant. Reason for failure was inaccurate target definition in only 2 cases. There were no bleeds, morbidity, or mortality after second RS. CONCLUSIONS: Second RS applied to previously treated CMs is safe and may be effective. Further investigations are needed to verify these findings and assess long-term benefit of second RS.

Contemporary radiosurgery of cerebral cavernous malformations: Part 1. Treatment outcome for critically located hemorrhagic lesions.

OBJECTIVELong-term benefits of radiosurgery (RS) applying modern protocols to treat cavernous malformations (CMs) remain unclear as critics may consider the decrease in the rebleed rate generally observed 2 years after RS as a reflection of the lesion's natural history. The authors adopted an early intention-to-treat attitude since rehemorrhage from deep-seated CMs ultimately leads to stepwise neurological deterioration. The safety of this early policy was previously demonstrated. Here, the authors revisit their current practice in a larger population with a longer follow-up time to assess the long-term effects of RS in the context of current knowledge on the natural history of CMs.METHODSThe authors conducted a retrospective analysis of 210 patients with 210 hemorrhagic CMs located in the brainstem, thalamus, or basal ganglia and treated with Gamma Knife RS between 1995 and 2014. Two hundred six patients had available follow-up, which was a median of 5.5 years (range 1-20 years). The median age was 37 years (0.5-77 years) at presentation and 43 (2-78) at treatment. One hundred twenty-seven CMs had bled once and 83 had had multiple hemorrhages prior to treatment.RESULTSThe lifetime annual bleed rate of CMs having a single hemorrhage prior to treatment was 2.4% per lesion. The hemorrhage rate stabilized at 1.1% after a temporary increase of 4.3% within the first 2 years after RS. The annual pretreatment hemorrhage rate was 2.8% for the lesions having multiple bleeds prior to RS with a pretreatment rebleed rate of 20.7% and with a modest gradual decrease within the first 5 years and remaining stable at 11.55% thereafter. The rebleed rate fell to 7.9% for the first 2 years after RS and declined further to 1.3% thereafter, which was significantly lower than the long-term pretreatment rebleed risk. The rate of hemorrhage-free survival remained 86.4% and 75.1% (1 patient each) at 20 years after RS in the single- and multiple-bleed groups, respectively.Pretreatment hemorrhages resulted in permanent deficits in 48.8% of the cases with a single bleed and in 77.1% of the cases with multiple bleeds. Both the rate and severity of deficits were significantly lower in the first group. Only mild and a low rate of permanent neurological deficits were caused either by posttreatment hemorrhages (7.4%) or by radiation (7.2%). The rate of persistent morbidity in the single-bleed group remained significantly lower at the end of the study than pretreatment morbidity in the multiple-bleed group (OR 2.9, 95% CI 1.6-5.3). Lesion-specific mortality was < 1%.CONCLUSIONSThe hemorrhage rate of CMs after RS remained low after the first 2 years during the longer follow-up period. The benefit of early treatment appears to be confirmed by the study results as repeated hemorrhages carry the risk of significantly higher cumulative morbidity than the morbidity associated with RS.

Contemporary radiosurgery of cerebral cavernous malformations: Part 2. Treatment outcome for hemispheric lesions.

OBJECTIVEThe role of radiosurgery (RS) in treating superficial cavernous malformations (CMs) is insufficiently studied in part because of the disappointing results of early experimental attempts as compared to the mostly safe and effective microsurgery. Nonetheless, because of lesion- or treatment-specific factors, a therapeutic alternative may be required. In this study, the authors aimed to assess the safety of RS in treating superficial CMs and to analyze its long-term effect on hemorrhage rates and epilepsy control.METHODSThe authors conducted a retrospective analysis of 96 patients with 109 CMs located in the cerebral or cerebellar hemispheres and treated with RS between 1995 and 2014. A median of 15 Gy (range 10-25 Gy) was given to the 50% prescription isodose level, lesion volume was 604 mm3 (4-8300 mm3), and the prescription isodose volume was 638.5 mm3 (4-9500 mm3). Outcomes were compared to those of 206 deep-seated lesions reported on in another study. Ninety-five patients had available follow-up, which was a median of 7 years (1-21 years). Median patient age was 42 years (0.5-77) at presentation and 45 (3-80) at treatment. Seventy-one CMs presented with symptomatic hemorrhage, and 52 caused seizures.RESULTSIn the nonhemorrhagic group (37 lesions), one bleed occurred during the follow-up period, for an annual bleed rate of 0.4% per lesion. The lifetime annual bleed rate of CMs having a single hemorrhage prior to treatment was 2.5%. The rebleed rate in the single-bleed group decreased from 1.8% within the first 2 years after RS to 0.7% thereafter. The pretreatment rebleed rate for lesions having multiple bleeds prior to RS was 14.15%, which fell to 3.85% for the first 2 years after RS and declined to 1.3% thereafter. Multivariate analysis showed younger age, deep lesion location, and multiple pretreatment hemorrhages as significant predictors of posttreatment hemorrhage.Pretreatment hemorrhages led to permanent deficits in 41.4% of the cases with a single bleed and in 46.1% of cases with multiple bleeds. Only mild (modified Rankin Scale score 1) and a low rate of permanent neurological deficits were caused either by posttreatment hemorrhages (4.3%) or by radiation (2%).The rate of improvement in epilepsy was 84.9% after RS in patients with at least one seizure prior to treatment, not depending on the presence of hemorrhage or the time interval between presentation and treatment. Favorable outcome occurred in 81% of patients whose seizures were not controlled with antiepileptic medication prior to RS.CONCLUSIONSRadiosurgery for superficial CMs is safe and appears to be effective, offering a real treatment alternative to surgery for selected patients. Given their relatively benign natural history, superficial CMs require further study to verify the long-term benefit of RS over the lesions' natural history.

Staged-Volume Radiosurgery of Large Arteriovenous Malformations Improves Outcome by Reducing the Rate of Adverse Radiation Effects.

Background: The treatment of large arteriovenous malformations (AVMs) remains challenging. Recently, staged-volume radiosurgery (SVRS) has become an option. Objective: To compare the outcome of SVRS on large AVMs with our historical, single-stage radiosurgery (SSRS) series. Methods: We have been prospectively collecting data of patients treated by SVRS since 2007. There were 84 patients who had a median age of 37 years (range, 9-62 years) who were treated until July 2013. The outcomes of 76 of those who had follow-ups available were analyzed and compared with the outcomes of 122 patients treated with the best SSRS technique. Results: There were 21.5% of AVMs that were deep seated, and 44% presented with hemorrhage resulting in 45% fixed neurological deficit. There were 14% of patients who had undergone embolization before radiosurgery. The median nidus treatment volume was 19.7 cm3 (6.65-68.7) and 17.5 Gy (13-22.5) prescription isodose was given. Of the 44 lesions having radiological follow-up at 4 years, 61.4% were completely obliterated. Previous embolization (50% with and 63% without) and higher Spetzler-Martin grades appeared to be the negative factors in successful obliteration, but treatment volume was not. Within 3 years after radiosurgery, the annual bleed rates of unruptured and previously ruptured AVMs were 3.2% and 5.6%, respectively. Three bleeds were fatal and 2 resulted in significant modified Rankin scale 3 morbidity. These rates differ little from SSRS. Temporary adverse radiation effects (AREs) did not change significantly, but permanent AREs dropped from 15% to 6.5% (P = .03) compared with SSRS. Conclusion: Obliteration and hemorrhage rates of large AVMs treated by SVRS are similar to historical SSRS. However, SVRS offers a lower rate of AREs.

Radiosurgery of isolated cerebral vessels following administration of paclitaxel in the rat.

OBJECT: Progressive obliteration occurs in arteriovenous malformations (AVMs) after radiosurgery; however, the risk of hemorrhage remains until the obliteration process is complete. The authors sought to enhance the radiation effect and reduce the risk of hemorrhage by facilitating faster vessel obliteration. To that end, a combination of a lower radiation dose with the addition of a radiosensitizing agent was compared with the effect of a higher radiation dose alone. METHODS: Using a method described by Mulvany and Halpern, isometric myography measurements were made on isolated rat middle cerebral artery specimens. The vessels were treated with 200 Gy, 80 Gy, 50 Gy, 25 Gy, 20 Gy, or 15 Gy by using Gamma Knife surgery. Taxol (paclitaxel 3 mg/kg/body weight) was administered intravenously to the animals. Survival times posttreatment were 24 hours, 6 weeks, 12 weeks, 12 months, or 18 months. After dissection, the middle cerebral arteries were mounted on a small-vessel myograph, and contraction and relaxation studies were performed. In a second series of experiments these results were validated in human fibroblast culture. When the cultures were 75 to 80% colonized, the samples were treated in vitro with 60Co gamma radiation in similar doses with or without paclitaxel. CONCLUSIONS: Constriction responses were generally decreased in the paclitaxel-treated vessels. Differences were significant at 6 weeks (p < 0.05) and at 1 year (p < 0.05). After 1 year, in the paclitaxel-treated groups vascular reactivity was completely abolished in vessels receiving 50 Gy. In comparison, it took 6 months longer (18 months) for this reaction to be abolished in vessels without paclitaxel treatment. In tissue cultures Giemsa staining and immunohistochemical reactions for p53, Ki-67, CD-34, and SMA antigens revealed marked fibroblast hypertrophy in all of the paclitaxel-treated groups. Paclitaxel-treated vessels demonstrated decreased reactivity at significantly earlier stages than vessels that had not been treated. It would appear that paclitaxel causes acceleration in the time course of the late biological effect of gamma radiation. This beneficial effect could be used in Gamma Knife surgery in patients with AVMs, thus reducing the risk of posttreatment hemorrhage.

Ultrastructural changes in arteriovenous malformations after gamma knife surgery: an electron microscopic study.

OBJECT: The authors analyzed morphological alterations at the subcellular level by undertaking transmission electron microscopy in arteriovenous malformations (AVMs) after gamma knife surgery (GKS). METHODS: Histological, immunohistochemical, and electron microscopic investigations were performed in a series of pathological specimens obtained in seven patients. The patients harbored cerebral AVMs that had been previously treated with GKS and had suffered subsequent bleeding 10 to 52 months after treatment. Histological studies revealed spindle cell proliferation in the connective tissue stroma and in the subendothelial region of the irradiated AVM vessels. Electron microscopy demonstrated different ultrastructural characteristics of this spindle cell population. There were cells with a smooth-edged oval nuclei surrounded by massive bundles of collagen fibers in the extracellular matrix. Other cells with the same nuclear morphology contained abundant intracytoplasmic filaments. Nuclear deformation was connected to a fibrillary system developed within the cytoplasm, and peripheral attachment sites were related to an extracellular layer of basement membrane-like material arranged parallel to the cell border. Also present were cells containing well-developed cisterns of rough endoplasmic reticulum and dense bodies at the periphery of the cytoplasm with folded, irregular nuclei. CONCLUSIONS: The ultrastructural and histological characteristics of the spindle cell population in the GKS-treated AVMs are similar to those designated as myofibroblasts in wound healing processes and pathological fibromatoses. Because similar cell modifications have not been demonstrated in control nonirradiated AVM specimens, these myofibroblasts may contribute to the shrinking process and final occlusion of AVMs after radiosurgery.

Rotational movements of the automatic positioning system under load and their significance for patient treatments.

OBJECT: During routine quality assurance (QA) testing of the gamma knife Automatic Positioning System (APS), it was noticed that slight pressure applied to the handle of the QA test tool produced visible rotation of the APS assembly. The authors describe the tests performed to quantify these movements. METHODS: A stereotactic frame was positioned in the slides of the APS and known loads applied using a spring balance to the upper corner of the frame. Movement at the corner of the frame (y = 200) was measured using a dial gauge. The typical load applied to the APS by a patient with a medium-sized head was determined in a treatment simulation. Projecting the measured data, a plot showing the resultant error in the position of a target point was constructed. Error values increased with distance from the frame, up to a maximum of 0.3 mm (at the superior limit of treatment range). Increased loads could be applied to the system during patient movements, and these would result in larger displacements. Two volunteers enlisted to simulate patient movements and the deflections were recorded. It was estimated that maximum errors in the target positioning of 0.45 mm might take place during these movements. CONCLUSIONS: The use of the APS has some additional and unexpected associated errors. The authors believe, however, that because the errors are smaller than those of target localization and manual trunnion treatments, its clinical use is still justified. The manufacturer is investigating the cause of the movements and possible solutions.

The commissioning and quality assurance of the Automatic Positioning System on the Leksell gamma knife.

OBJECT: The authors describe a series of commissioning checks that were developed following the installation of the Automatic Positioning System (APS) on the model C gamma knife. METHODS: System reliability was checked by performing a series of test treatments using the APS. A phantom was designed to enable the exposure of small pieces of Gaf Chromic film at 40 different predefined x, y, and z coordinates. The phantom consisted of a base plate with a series of film holders to facilitate the exposures using a 4-mm field, the center of which was marked. A spreadsheet calculation was performed to verify the conversion from Leksell coordinates to the APS coordinates when the treatment angle (gamma angle) is other than 90 degrees. A number of APS plans were prepared and the coordinate transformation verified. Precision measurements were performed to verify the correct positioning of the high bars when attached to the frame. The Gaf Chromic films were exposed, and the APS plans were used when confined to positions within the high bar range. A test tool to verify accurate location of the high bars on the frame was also designed. CONCLUSIONS: The performance of APS was verified independently of the manufacturer by using specially designed tools, phantoms, and spread sheets. At all points tested, the positional accuracy was found to be within specification. Conversion to APS coordinates was verified as correct.