A Retrospective Analysis of the Role of Single-Session Gamma Knife Stereotactic Radiosurgery in Sporadic Vestibular Schwannomas with Tumor Volumes Greater Than 10 cm3: Is It Worth Stretching the Boundaries?

OBJECTIVE: To evaluate the role of single-session Gamma Knife stereotactic radiosurgery (GK-SRS) in the treatment of vestibular schwannomas (VSs) with volumes of greater 10 cm3. METHODS: A retrospective analysis was performed of 103 patients treated with single-session GK-SRS between 1993 and 2011 with a mean follow-up of 6.2 years ± 4.4 SD. Treatment, clinical and outcome details were recorded and assessed. RESULTS: Eighty-one (78.6%) patients achieved radiological control with slow progression in a further 5 (4.9%) patients, who did not require further treatment. Linear measurements did not correlate well with volume, which can predict outcome following treatment more precisely. 2.9% of patients developed a new facial paresis, 5.8% trigeminal numbness and 2.9% facial pain. In all, 26 (25.2%) patients who were tested preserved some level of hearing following treatment. CONCLUSIONS: The overall radiological control rate in this study was 78.6%, while tumor volumes less than 20 cm3 can be safely treated with single-stage GK-SRS with an expected control rate of 83.2% without unacceptable morbidity rates. GK-SRS can be utilized as a first-line treatment option in patients with large-volume VSs especially in whom surgery is unattractive.

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.

Stereotactic radiosurgery for arteriovenous malformations located in deep critical regions.

BACKGROUND: Radiosurgery is widely used to treat deep eloquent arteriovenous malformations (AVMs). OBJECTIVE: To evaluate how anatomic location, AVM size, and treatment parameters define outcome. METHODS: Retrospective analysis of 356 thalamic/basal ganglia and 160 brainstem AVMs treated with gamma knife radiosurgery. RESULTS: Median volume was 2 cm (range, 0.02-50) for supratentorial and 0.5 cm (range, 0.01-40) for brainstem AVMs; the marginal treatment doses were 17.5 to 25 Gy. After single treatment, obliteration was achieved in 65% of the brainstem, in 69% of the supratentorial, and 40% of the peritectal AVMs. Obliteration of lesions <4 cm was better in the brainstem (70%) and in the supratentorium (80%), but not in the peritectal region (40%). Complications were rare (6%-15%) and mild (≤ modified Rankin scale [MRS] 2). Rebleed rate increased with size, but was not higher than before treatment. AVMs >4 cm in the brainstem were treated with unacceptable morbidity and low cure rate. Obliteration of large supratentorial AVMs was 65% to 47% with more complications ≥ MRS3. Repeat radiosurgical treatment led to obliteration in 66% of the cases with minor morbidity. CONCLUSION: Deep eloquent AVMs <4 cm can be treated safely and effectively with radiosurgery. Obliteration of peritectal AVMs is significantly lower after a single treatment. However, morbidity is low, and repeat treatment leads to good obliteration. Radiosurgical treatment >4 cm in the brainstem is not recommended. Supratentorial deep AVMs >8 cm can be treated with radiosurgery with higher risk and lower obliteration rate. However, these lesions are difficult to treat with other treatment modalities, and a 50% success rate makes radiosurgery a good alternative even in this challenging 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.

Stereotactic radiosurgery for deep-seated cavernous malformations: a move toward more active, early intervention. Clinical article.

OBJECT: The role of radiosurgery in the treatment of cavernous malformations (CMs) remains controversial. It is frequently recommended only for inoperable lesions that have bled at least twice. Rehemorrhage can carry a substantial risk of morbidity, however. The authors reviewed their practice of treating deep-seated inoperable CMs to assess the complication rate of radiosurgery, the impact that radiosurgery might have on rebleeding, and whether a more active, earlier intervention is justified in managing this condition. METHODS: The authors performed a retrospective analysis of 113 patients with 79 brainstem and 39 thalamic/basal ganglia CMs treated with Gamma Knife surgery. Lesions were stratified into 2 groups: those that might be lower risk with no more than 1 symptomatic bleed before radiosurgical treatment and those deemed high risk with multiple symptomatic hemorrhages before treatment. RESULTS: Forty-one CMs had multiple symptomatic hemorrhages before radiosurgery with a first-ever bleed rate of 2.9% per lesion per year, a rebleed rate of 30.5% per lesion per year, and a median time of 1.5 years between the first and second bleeds. In this group the rebleed rate decreased to 15% for the first 2 years after radiosurgery and declined further to 2.4% thereafter. Pretreatment multiple bleeds led to persistent deficits in 72% of the patients. Seventy-seven CMs had no more than 1 symptomatic bleed before radiosurgery, making for a lifetime bleed rate of 2.2% per lesion per year. The short period between the presenting bleed and treatment (median 1 year) makes the natural history in this group uncertain. The rate of hemorrhage in the first 2 years after treatment was 5.1%, and 1.3% thereafter. Pretreatment hemorrhages resulted in permanent deficits in 43% of the patients in this group, a rate significantly lower than in the multiple-bleeds group (p < 0.001). Posttreatment hemorrhages led to persistent deficits in only 7.3% of the patients. Permanent adverse radiation effects were rare (7.3%) and minor in both groups. CONCLUSIONS: Stereotactic radiosurgery is a safe management strategy for CMs in eloquent sites with the marked advantage of reducing rebleed risks in patients with repeated pretreatment hemorrhages. The benefit in treating CMs with a single bleed is less clear. Note, however, that repeated hemorrhage carries a significant risk of increased morbidity far in excess of any radiosurgery-related morbidity, and the authors assert that this finding justifies the early active management of deep-seated CMs.

The clinical course after stereotactic radiosurgical amygdalohippocampectomy with neuroradiological correlates.

OBJECTIVE: Radiosurgical ablation of the mesial temporal lobe structures can be used in the treatment of intractable temporal lobe epilepsy associated with mesial temporal sclerosis. In this study, we analyzed the magnetic resonance imaging (MRI) and spectroscopic changes that follow the treatment and report the clinical sequelae of the procedure. METHODS: Eight patients (five men and three women; age, 38 +/- 15 yr [mean +/- standard deviation]) with mesial temporal sclerosis were treated with radiosurgical amygdalohippocampectomy (25 Gy to the 50% isodose region with a mean target volume of 6.2 +/- 0.7 cm). MRI and magnetic resonance spectroscopy were performed sequentially during a 24-month period after treatment. RESULTS: Patients were followed up clinically for 24 to 53 months. MRI scans revealed changes of marked temporal lobe swelling, with often markedly elevated apparent diffusion coefficients in keeping with vasogenic edema that became apparent 6 to 12 months after stereotactic radiosurgery. Spectroscopy of the target area revealed a progressive loss of N-acetylaspartate (the late evolution of lactate) and a peak in the choline-to-creatine ratio that seemed to coincide with the peak of the vasogenic edema in the temporal lobe surrounding the target area. Clinically, all patients showed some reduction in seizure frequency, although in two patients, this reduction was modest. The MRI changes in those patients were also modest, and three patients ultimately became free of seizures. However, there was a latency of 18 to 24 months before improvements in seizure control occurred, and during this period, seizures worsened or changed in four patients. Two patients also developed symptoms of increased intracranial pressure with mild dysphasia, which responded to administration of corticosteroid medication. However, no long-term clinical verbal memory decline was identified in any patient. CONCLUSION: There are marked changes in MRI scans and magnetic resonance spectroscopic findings after patients undergo radiosurgery for temporal lobe epilepsy. Our initial findings suggest that some patients may have a period of distressing symptoms that accompany changes that are visualized on the MRI scans.

Gamma Knife treatment for cerebral arteriovenous malformations.

One of the earliest indications for Gamma Knife treatment, radiosurgery for cerebral arteriovenous malformations, has stood the test of time. While initially only the ideal cases (small, compact nidus in a non-eloquent site) were chosen, increasingly larger, more complex AVMs were treated. Combination treatment with embolisation and surgery enables most lesions to be treated with success and remarkably low complication rate. This paper is a brief overview of the experience gained in Sheffield.

Radiosurgical planning of meningiomas: compromises with conformity.

The radiosurgical planning of meningiomas frequently necessitates compromises between irradiating tumour and risking damage to adjacent structures. In selected cases, we resolved this by excluding part of the tumour from the prescription isodose volume. Most of these compromises or 'suboptimal' plans achieved growth control. Growth control could not be related to conformity indices or to various measures of the radiation dose received by the meningioma. Examining recurrences, 75% arose from dura outside the original treatment field. These findings are discussed in terms of dose prescription protocols and the use of conformity indices in planning. The importance of the dural origin of meningiomas is well established in surgical practice, as reflected by Simpson's grades, but may be equally significant in radiosurgical practice.

Involvement of the medial pallidum in focal myoclonic dystonia: A clinical and neurophysiological case study.

We successfully treated a patient with familial myoclonic dystonia (FMD), which primarily affected his neck muscles, with bilateral deep brain stimulation (DBS) to the medial pallidum, and investigated the role of the medial pallidum in FMD. A patient with FMD underwent bilateral implantation of DBS electrodes during which field potentials (FPs) in the medial pallidum and electromyograms (EMGs) from the affected neck muscles were recorded. The effects of high-frequency DBS to the medial pallidum on the FMD were also assessed by recording EMGs during and immediately after implantation, as well as 6 days and 8 weeks postoperatively. During spontaneous myoclonic episodes, increased FPs oscillating at 4 and 8 Hz were recorded from the medial pallidum; these correlated strongly with phasic EMG activity at the same frequencies in the contralateral affected muscles. The EMG activity was suppressed by stimulating the contralateral medial pallidum at 100 Hz during the operation and continuous bilateral DBS from an implanted stimulator abolished myoclonic activity even more effectively postoperatively. The phasic pallidal activity correlated with and led the myoclonic muscle activity, and the myoclonus was suppressed by bilateral pallidal DBS, suggesting that the medial pallidum was involved in the generation of the myoclonic activity. High-frequency DBS may suppress the myoclonus by desynchronising abnormal pallidal oscillations. This case study has significant clinical implications, because at present, there is no effective treatment for focal myoclonic dystonia.

Stereotactic radiosurgery for type 2 neurofibromatosis acoustic neuromas: patient selection and tumour size.

Acoustic neuromas which are secondary to type 2 neurofibromatosis (NF2) respond less well to radiosurgery than unilateral sporadic disease. To refine the selection of these patients, a regression analysis was performed examining the response to radiosurgery of 114 NF2 tumours. The major determinant of outcome was tumour volume (p < 0.001). Calculating sensitivity and specificity values for different tumour volume limits gives a sensitivity value of 0.96 for a volume limit of 10 cm(3). This suggests that the size constraints that apply to the radiosurgical management of NF2 acoustic neuromas differ and are more restricted than those which are accepted for acoustic neuromas in general.