Fragile X-associated tremor/ataxia syndrome treated with multitarget deep brain stimulation.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive hereditary neurodegenerative disorder which causes intention tremor and cerebellar ataxia. It typically affects the ageing population. Deep brain stimulation (DBS) is widely accepted in the treatment of common movement disorders and has been trialled in treating rare and complex neurodegenerative disorders. We report a case of a man in his 40s with a long history of tremor affecting his hands. MRI brain revealed high T2 signal in the middle cerebellar peduncles. Genetic testing revealed FMR1 premutation confirming the diagnosis of FXTAS. Subsequently, he was treated with multitarget DBS of the ventralis intermediate nucleus and ventralis oralis posterior nuclei bilaterally, with excellent neurological function at 9 years follow-up. This case suggests multitarget DBS for FXTAS with neurophysiology-guided DBS programming can provide excellent long-term tremor suppression in selected patients.

Neuro-Ophthalmic Complications of Vestibular Schwannoma Resection: Current Perspectives.

Vestibular schwannomas (VSs), also called acoustic neuromas, are benign intracranial neoplasms of the vestibulocochlear (VIII) cranial nerve. Management options include "wait-and-scan," stereotactic radiosurgery and surgical resection. Due to the proximity of the VIII nerve to the facial (VII) nerve in the cerebello-pontine angle, the VII nerve is particularly vulnerable to the effects of surgical resection. This can result in poor eye closure, lagophthalmos and resultant corneal exposure post VS resection. Additionally, compression from the tumor or resection can cause trigeminal (V) nerve damage and a desensate cornea. The combination of an exposed and desensate cornea puts the eye at risk of serious ocular complications including persistent epithelial defects, corneal ulceration, corneal vascularization, corneal melting and potential perforation. The abducens (VI) nerve can be affected by a large intracranial VS causing raised intracranial pressure (a false localizing sign) or as a result of damage to the VI nerve at the time of resection. Other types of neurogenic strabismus are rare and typically transient. Contralaterally beating nystagmus as a consequence of vestibular dysfunction is common post-operatively. This generally settles to pre-operative levels as central compensation occurs. Ipsilaterally beating nystagmus post-operatively should prompt investigation for post-operative cerebrovascular complications. Papilledema (and subsequent optic atrophy) can occur as a result of a large VS causing raised intracranial pressure. Where papilledema follows surgical resection of a VS, it can indicate that cerebral venous sinus thrombosis has occurred. Poor visual function following VS resection can result as a combination of all these potential complications and is more likely with larger tumors.

To suture or not to suture? Does globe immobilisation technique affect clinical outcome in stereotactic radiosurgery for uveal melanoma?

INTRODUCTION: Stereotactic radiosurgery (SRS) is a valuable treatment option for uveal melanoma, offering excellent tumour control rates and eye preservation. Its efficacy relies upon accurate localisation of the tumour, which is challenging in the mobile eye. Various methods of globe immobilisation have been used, including non-invasive devices, such as eye movement tracking and suction cups, but common practice is to use local anaesthetic block with or without transconjunctival suturing of the extraocular muscles. Some studies have suggested that the addition of muscle suturing to local anaesthetic block provides better immobilisation of the globe, when compared to anaesthetic block alone. Controversy exists regarding the clinical relevance of this observation and ocular oncologists differ in their choice of immobilisation technique. METHODS: In order to establish if the addition of muscle suturing to local anaesthetic block improves clinical outcomes, we performed a retrospective review of all cases that underwent SRS for uveal melanoma over a 10-year period (May 2008 to May 2018). Based on surgeon preference, all patients received either local anaesthetic block plus muscle suturing (Group A) or local anaesthetic block alone (Group B) to induce globe akinesia. Outcomes assessed were primary treatment failure, tumour recurrence, secondary enucleation and death rate. RESULTS: In our cohort of 290 eyes; 118 patients were in group A and 172 patients were in group B. There were no cases of primary treatment failure in either group. With a minimum of 24 months follow-up, only 3 patients experienced tumour recurrence (1 in group A and 2 in group B). There was no significant difference in recurrence, enucleation and all-cause death rates between the two groups. CONCLUSION: Our retrospective review suggests that although extraocular muscle suturing may be considered by some units to provide superior globe immobilisation for SRS, it does not alter the clinical outcome.

Long-term safety of gamma knife radiosurgery (SRS) for acromegaly.

PURPOSE: Acromegaly has high morbidity and mortality when growth hormone secretion remains uncontrolled. Stereotactic radiosurgery (SRS) may be used when pituitary surgery is not suitable or unsuccessful, but there are few very long-term safety data available, especially for significant adverse events such as stroke. METHODS: 118 patients with acromegaly were treated with SRS between 1985 and 2015, at the National Centre for Stereotactic Radiosurgery, Sheffield, UK. Data were gathered from case notes, hospital databases, and patient questionnaires. Stroke incidence in comparison to the normal population was quantified using the standardised incidence ratio (SIR), and visual complications assessed. RESULTS: 88% (104/118) had complete morbidity follow up data for analysis. The mean follow-up was 134 months, and median SRS dose was 30 Gy. 81% of tumours had cavernous sinus invasion. There was no excess stroke rate relative to that seen in two age- and sex-matched large population studies (SIR = 1.36, 95% CI 0.27-3.96; SIR = 0.52, 95% CI 0.06-1.89). In 68/104 patients who had MRI-guided SRS with no further radiation treatment (SRS or fractionated radiotherapy) there was no loss of visual acuity and 3% developed ophthalmoplegia. There was a positive correlation between > 1 radiation treatment and both ophthalmoplegia and worsening visual acuity. CONCLUSION: Stroke rate is not increased by SRS for acromegaly. Accurate MRI-based treatment planning and single SRS treatment allow the lowest complication rates. More than one radiation treatment (SRS or fractionated radiotherapy) was associated with increased visual complications.

Gamma Knife Stereotactic Radiosurgery for the treatment of chordomas and chondrosarcomas.

INTRODUCTION: Primary chordomas and chondrosarcomas of the skull base are difficult tumours to treat successfully. Despite advances in surgical techniques, a gross total resection is often impossible to achieve. In addition, some patients may be deemed unsuitable or not wish to undergo extensive surgery for these conditions. This study examines the role of Gamma Knife Stereotactic Radiosurgery (GKRS) in the treatment of these difficult cases. METHODS: All patients harbouring either a chordoma or chondrosarcoma treated at the National Centre for Stereotactic Radiosurgery, Royal Hallamshire Hospital, Sheffield, UK, between 1985 and 2018, were reviewed with regard to their clinical presentations, pre- and post-treatment imaging, GKRS prescriptions and outcomes. RESULTS: In total, 24 patients with a mean tumour volume of 13 cm3 in the chordoma group (n=15) and 12 cm3 in the chondrosarcoma group (n=9) underwent GKRS. The 5- and 10-year overall survival rates for the chordoma group were 67% and 53% respectively, while for the chondrosarcoma group, they were 78% at both time points. The tumour control rates at 5 and 10 years in the chordoma group were 67% and 49% and for the chondrosarcoma group 78% at both time points. Patients with tumour volumes of less than 7 cm3 before GKRS treatment demonstrated a statistically significant longer overall survival rate (p=0.03). CONCLUSIONS: GKRS offers a comparable option to proton beam therapy for the treatment of these tumours. Early intervention for tumour volumes of less than 7 cm3 gives the best long-term survival rates.

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.

Tremor after long term lithium treatment; is it cortical myoclonus?

INTRODUCTION: Tremor is a common side effect of treatment with lithium. Its characteristics can vary and when less rhythmical, distinction from myoclonus can be difficult. METHODS: We identified 8 patients on long-term treatment with lithium that developed upper limb tremor. All patients were assessed clinically and electrophysiologically, with jerk-locked averaging (JLA) and cross-correlation (CC) analysis, and five of them underwent brain MRI examination including spectroscopy (MRS) of the cerebellum. RESULTS: Seven patients (6 female) had action and postural myoclonus and one a regular postural and kinetic tremor that persisted at rest. Mean age at presentation was 58 years (range 42-77) after lengthy exposure to lithium (range 7-40 years). During routine monitoring all patients had lithium levels within the recommended therapeutic range (0.4-1 mmol/l). There was clinical and/or radiological evidence (on cerebellar MRS) of cerebellar dysfunction in 6 patients. JLA and/or CC suggested a cortical generator of the myoclonus in seven patients. All seven were on antidepressants and three additionally on neuroleptics, four of them had gluten sensitivity and two reported alcohol abuse. CONCLUSIONS: A synergistic effect of different factors appears to be contributing to the development of cortical myoclonus after chronic exposure to lithium. We hypothesise that the cerebellum is involved in the generation of cortical myoclonus in these cases and factors aetiologically linked to cerebellar pathology like gluten sensitivity and alcohol abuse may play a role in the development of myoclonus. Despite the very limited evidence in the literature, lithium induced cortical myoclonus may not be so rare.

Radiosurgery as primary management for acromegaly.

OBJECTIVE: Transsphenoidal surgery (TSS) remains the recommended primary treatment for acromegaly. Long-term outcome data are not available for patients treated with gamma knife radiosurgery (STRS) as a primary treatment. DESIGN: Retrospective cohort study. DATA COLLECTION: notes review, laboratory results, general physician notes, patient questionnaire and death certification. PATIENTS: Twenty acromegaly patients underwent primary STRS at the National Centre for Radiosurgery, Sheffield, UK, between 1985 and 2015. MEASUREMENTS: Biochemical control (GH/IGF1), hypopituitarism, morbidity and mortality were all recorded. RESULTS: At 20 years of follow-up, control was seen in all on acromegaly-specific medication (n = 12) and 75% of those off medication (3/4). Time for 50% to achieve control on medication was 3 years, and 7.4 years off medication. Median marginal radiation dose was 27.5 Gy, and median follow-up was 166.5 months. 53% of patients developed new hypopituitarism at a median follow-up of 146 months, and the development of first onset of hypopituitarism occurred as late as 20 years after treatment. With MRI planning, no other complications were noted. Three patients underwent subsequent TSS due to poor biochemical control. During follow-up, 7 patients died at a median age of 65 years. There were no STRS-related deaths. CONCLUSION: This is the longest follow-up of patients who have undergone primary STRS for acromegaly. It shows low morbidity, but significant latency to biochemical control and new-onset hypopituitarism. This mandates very long-term follow-up for these patients. STRS has shown good long-term efficacy providing initial control can be afforded by optimal medical management. While TSS remains best practice, STRS offers an alternative for those in whom surgery is not an option.

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.

The cortical focus in childhood absence epilepsy; evidence from nonlinear analysis of scalp EEG recordings.

OBJECTIVE: To determine the origin and dynamic characteristics of the generalised hyper-synchronous spike and wave (SW) discharges in childhood absence epilepsy (CAE). METHODS: We applied nonlinear methods, the error reduction ratio (ERR) causality test and cross-frequency analysis, with a nonlinear autoregressive exogenous (NARX) model, to electroencephalograms (EEGs) from CAE, selected with stringent electro-clinical criteria (17 cases, 42 absences). We analysed the pre-ictal and ictal strength of association between homologous and heterologous EEG derivations and estimated the direction of synchronisation and corresponding time lags. RESULTS: A frontal/fronto-central onset of the absences is detected in 13 of the 17 cases with the highest ictal strength of association between homologous frontal followed by centro-temporal and fronto-central areas. Delays consistently in excess of 4 ms occur at the very onset between these regions, swiftly followed by the emergence of "isochronous" (0-2 ms) synchronisation but dynamic time lag changes occur during SW discharges. CONCLUSIONS: In absences an initial cortico-cortical spread leads to dynamic lag changes to include periods of isochronous interhemispheric synchronisation, which we hypothesize is mediated by the thalamus. SIGNIFICANCE: Absences from CAE show ictal epileptic network dynamics remarkably similar to those observed in WAG/Rij rats which guided the formulation of the cortical focus theory.

Gamma Knife radiosurgery for glomus jugulare tumors: a single-center series of 75 cases.

OBJECTIVE Glomus jugulare tumors are rare indolent tumors that frequently involve the lower cranial nerves (CNs). Complete resection can be difficult and associated with lower CN injury. Gamma Knife radiosurgery (GKRS) has established its role as a noninvasive alternative treatment option for these often formidable lesions. The authors aimed to review their experience at the National Centre for Stereotactic Radiosurgery, Sheffield, United Kingdom, specifically the long-term tumor control rate and complications of GKRS for these lesions. METHODS Clinical and radiological data were retrospectively reviewed for patients treated between March 1994 and December 2010. Data were available for 75 patients harboring 76 tumors. The tumors in 3 patients were treated in 2 stages. Familial and/or hereditary history was noted in 12 patients, 2 of whom had catecholamine-secreting and/or active tumors. Gamma Knife radiosurgery was the primary treatment modality in 47 patients (63%). The median age at the time of treatment was 55 years. The median tumor volume was 7 cm3, and the median radiosurgical dose to the tumor margin was 18 Gy (range 12-25 Gy). The median duration of radiological follow-up was 51.5 months (range 12-230 months), and the median clinical follow-up was 38.5 months (range 6-223 months). RESULTS The overall tumor control rate was 93.4% with low CN morbidity. Improvement of preexisting deficits was noted in 15 patients (20%). A stationary clinical course and no progression of symptoms were noted in 48 patients (64%). Twelve patients (16%) had new symptoms or progression of their preexisting symptoms. The Kaplan-Meier actuarial tumor control rate was 92.2% at 5 years and 86.3% at 10 years. CONCLUSIONS Gamma Knife radiosurgery offers a risk-versus-benefit treatment option with very low CN morbidity and stable long-term results.

Clinical Experience with Pedunculopontine Nucleus Stimulation in Conditions with Nigrostriatal Disconnection.

BACKGROUND: The pedunculopontine nucleus (PPN) is a part of the mesencephalic locomotor region and, in recent years, it has been considered a new surgical target for deep brain stimulation (DBS) for movement disorders including atypical parkinsonian syndromes such as progressive supranuclear palsy (PSP) and multiple system atrophy. Involvement of the PPN may play an important role in gait impairment in these disorders and the development of PPN DBS could potentially provide treatment for this disabling problem. However, the role of the PPN and the specific pathways involved in gait control and other motor functions are poorly understood. METHODS: We present a chronological account of our group's experience in the use of PPN DBS. This entails the treatment of four patients with disabling movement disorders who all exhibited either marked damage or disconnection of the nigro-striatal pathway. RESULTS: Within our series, the results were variable in that 2 of the 4 patients benefited greatly from DBS but the other 2 did not. CONCLUSIONS: Our findings suggest that in carefully selected patients, PPN DBS can potentially alleviate symptoms due to dopaminergic striatal inactivity; symptoms that are typically resistant to stimulation of other subcortical targets used for parkinsonian syndromes and movement disorders.

Cryotherapy increases features of plaque stability in atherosclerotic rabbits.

AIMS: In the last 10 years, cryotherapy has been investigated as a new technology to treat vascular disease. The efficiency of cryotherapy in stabilising atherosclerotic plaques has never been described. The purpose of the present study was to evaluate the effect of catheter-based cryotherapy on atherosclerotic plaque composition in a rabbit model of atherosclerosis. METHODS AND RESULTS: Twenty-four New Zealand white rabbits were fed a 0.3% cholesterol-supplemented diet for 24 weeks. At two predefined sites of the atherosclerotic thoracic aorta, catheter-based cryotherapy, applying either single-dose, double-dose cryotherapy or control inflation, was performed after randomisation. Rabbits were continued on a cholesterol-supplemented diet for one day (acute) or four weeks (chronic). One day after cryotherapy, apoptotic cell death of smooth muscle cells (SMCs) and endothelial cells (ECs) was observed, whereas macrophages were unaffected. Four weeks later, the amount of SMCs was restored, the EC layer was regenerated, and a subendothelial macrophage-free layer was formed, indicative of a more stable plaque. In addition, both the thickness and the type I collagen content of the fibrous cap were increased. CONCLUSIONS: The present study demonstrated that cryotherapy is feasible and appears to stabilise atherosclerotic plaques in a rabbit model.

Gamma knife surgery for pediatric arteriovenous malformations: a 25-year retrospective study.

OBJECT: The authors present their 25-year experience in treating pediatric arteriovenous malformations (AVMs) to allow comparisons with other historic studies and data in adults. METHODS: Data were collected from a prospectively maintained departmental database selected for age and supplemented by case note review and telephone interviews as appropriate. RESULTS: Three hundred sixty-three patients, ages 1-16 years (mean ± SD, 12 ± 3.2 years), underwent 410 treatments; 4 had planned 2-stage treatments and 43 were retreated subsequent to an initial partial response. Fifty-eight percent received general anesthesia for the procedure. Sixteen percent had previously undergone embolization. The most common presenting symptoms were as follows: hemorrhage (80.2%), epilepsy (8.3%; overall seizure prevalence 19.9%), and migrainous headaches (6.3%). Only 0.28% of the AVMs were incidental findings. The mean lesion volume was 3.75 ± 5.3 cm3 (range 0.01-32.8 cm3), with a median Spetzler-Martin grade of III (range I-V). The mean peripheral (therapeutic) dose was 22.7 ± 2.3 Gy (range 15-25 Gy), corresponding to a mean maximum dose of 43.6 ± 6 Gy (range 25-51.4 Gy). The obliteration rate was 71.3% in patients who received one treatment and 62.5% for retreated patients, with a mean obliteration time of 32.4 and 79.6 months, respectively. The overall obliteration rate was 82.7%. No follow-up data are as yet available for the 4 patients who underwent the staged treatments. Only 4 patients received peripheral doses below 20 Gy, and the AVM was obliterated in 3 of these patients. The other patients received 20, 22.5, or 25 Gy and had obliteration rates of 82.6%, 77.7%, and 86.3%, respectively. The bleeding rate postradiosurgery was 2.2%, and the cumulative complication rate was 3.6%, with radionecrosis being the most common complication (1.1%). CONCLUSIONS: Surprisingly, there was no correlation (p = 0.43) between outcome and radiosurgical dose when that dose was between 20 and 25 Gy, thus suggesting that the lower of these 2 doses may be effective. Radiosurgery for pediatric AVM is safe and effective.

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 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.