Fetal Dose Evaluation for Pregnant Patients on Leksell Gamma Knife Perfexion/Icon.

INTRODUCTION: It is a normal procedure to avoid the application of ionizing radiation during pregnancy. In very rare occasions, treatment can be performed, but doses to the fetus must be evaluated and reported, and the patient must sign informed consent. There can occur two types of damage caused by ionizing radiation - deterministic and stochastic effects. Deterministic effects may occur after reaching a certain threshold (100 mGy for this study); meanwhile, stochastic effects have no limit and their probability rises with dose. This study focuses on deterministic effects. CASE PRESENTATIONS: This study compares the dose measured on phantom for the area of the pelvis and the dose measured on 3 patients with dosimeters positioned on the pelvis irradiated on Leksell Gamma Knife Perfexion/Icon. The mean dose for measurement on phantom for the pelvis was 0.73 ± 0.76 mGy, and for the patients, it was 1.28 mGy, 0.493 mGy, and 0.549 mGy which is 80 times lower, 200 times lower, and 180 times lower than the threshold for deterministic effects, respectively. CONCLUSION: The measurement carried on phantom served as the base for drafting informed consent and provided initial proof that treatment can be safely delivered. Measurements performed on patients only confirmed that irradiation of pregnant patients on Leksell Gamma Knife Perfexion/Icon is safe relative to the deterministic effects. Nevertheless, pregnant patients should be treated with ionizing radiation only in very extraordinary situations.

Outcome Evaluation of Repeat Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations.

BACKGROUND: Repeat stereotactic radiosurgery (SRS) for persistent cerebral arteriovenous malformation (AVM) has generally favorable patient outcomes. However, reporting studies are limited by small patient numbers and single-institution biases. The purpose of this study was to provide the combined experience of multiple centers, in an effort to fully define the role of repeat SRS for patients with arteriovenous malformation. METHODS: This multicenter, retrospective cohort study included patients treated with repeat, single-fraction SRS between 1987 and 2022. Follow-up began at repeat SRS. The primary outcome was a favorable patient outcome, defined as a composite of nidus obliteration in the absence of hemorrhage or radiation-induced neurological deterioration. Secondary outcomes were obliteration, hemorrhage risk, and symptomatic radiation-induced changes. Competing risk analysis was performed to compute yearly rates and identify predictors for each outcome. RESULTS: The cohort comprised 505 patients (254 [50.3%] males; median [interquartile range] age, 34 [15] years) from 14 centers. The median clinical and magnetic resonance imaging follow-up was 52 (interquartile range, 61) and 47 (interquartile range, 52) months, respectively. At last follow-up, favorable outcome was achieved by 268 (53.1%) patients (5-year probability, 50% [95% CI, 45%-55%]) and obliteration by 300 (59.4%) patients (5-year probability, 56% [95% CI, 51%-61%]). Twenty-eight patients (5.6%) experienced post-SRS hemorrhage with an annual incidence rate of 1.38 per 100 patient-years. Symptomatic radiation-induced changes were evident in 28 (5.6%) patients, with most occurring in the first 3 years. Larger nidus volumes (between 2 and 4 cm3, subdistribution hazard, 0.61 [95% CI, 0.44-0.86]; P=0.005; >4 cm3, subdistribution hazard, 0.47 [95% CI, 0.32-0.7]; P<0.001) and brainstem/basal ganglia involvement (subdistribution hazard, 0.6 [95% CI, 0.45-0.81]; P<0.001) were associated with reduced probability of favorable outcome. CONCLUSIONS: Repeat SRS confers reasonable obliteration rates with a low complication risk. With most complications occurring in the first 3 years, extending the latency period to 5 years generally increases the rate of favorable patient outcomes and reduces the necessity of a third intervention.

Hemorrhage and Recurrence of Obliterated Brain Arteriovenous Malformations Treated With Stereotactic Radiosurgery.

BACKGROUND: Although complete nidal obliteration of brain arteriovenous malformations (AVM) is generally presumed to represent durable cure, postobliteration hemorrhage, and AVM recurrence have become increasingly recognized phenomena. The goal of the study was to define hemorrhage and nidal recurrence risks of obliterated AVMs treated with stereotactic radiosurgery (SRS). METHODS: This is a retrospective cohort study from the International Radiosurgery Research Foundation comprising AVM patients treated between 1987 and 2020. Patients with AVM obliteration on digital subtraction angiography (DSA) were included. Outcomes were (1) hemorrhage and (2) AVM recurrence. Follow-up duration began at the time of AVM obliteration and was censored at subsequent hemorrhage, AVM recurrence, additional AVM treatment, or loss to follow-up. Annualized risk and survival analyses were performed. A sensitivity analysis comprising patients with AVM obliteration on magnetic resonance imaging or DSA was also performed for postobliteration hemorrhage. RESULTS: The study cohort comprised 1632 SRS-treated patients with AVM obliteration on DSA. Pediatric patients comprised 15% of the cohort, and 42% of AVMs were previously ruptured. The mean imaging follow-up after AVM obliteration was 22 months. Among 1607 patients with DSA-confirmed AVM obliteration, 16 hemorrhages (1.0%) occurred over 2223 patient-years of follow-up (0.72%/y). Of the 1543 patients with DSA-confirmed AVM obliteration, 5 AVM recurrences (0.32%) occurred over 2071 patient-years of follow-up (0.24%/y). Of the 16 patients with postobliteration hemorrhage, AVM recurrence was identified in 2 (12.5%). In the sensitivity analysis comprising 1939 patients with post-SRS AVM obliteration on magnetic resonance imaging or DSA, 16 hemorrhages (0.83%) occurred over 2560 patient-years of follow-up (0.63%/y). CONCLUSIONS: Intracranial hemorrhage and recurrent arteriovenous shunting after complete nidal obliteration are rare in AVM patients treated with SRS, and each phenomenon harbors an annual risk of <1%. Although routine postobliteration DSA cannot be recommended to SRS-treated AVM patients, long-term neuroimaging may be advisable in these patients.

Stereotactic radiosurgery versus active surveillance for asymptomatic, skull-based meningiomas: an international, multicenter matched cohort study.

OBJECTIVE: The optimal management of asymptomatic, skull-based meningiomas is not well defined. The aim of this study is to compare the imaging and clinical outcomes of patients with asymptomatic, skull-based meningiomas managed either with upfront stereotactic radiosurgery (SRS) or active surveillance. METHODS: This retrospective, multicenter study involved patients with asymptomatic, skull-based meningiomas. The study end-points included local tumor control and the development of new neurological deficits attributable to the tumor. Factors associated with tumor progression and neurological morbidity were also analyzed. RESULTS: The combined unmatched cohort included 417 patients. Following propensity score matching for age, tumor volume, and follow-up 110 patients remained in each cohort. Tumor control was achieved in 98.2% and 61.8% of the SRS and active surveillance cohorts, respectively. SRS was associated with superior local tumor control (p < 0.001, HR = 0.01, 95% CI = 0.002-0.13) compared to active surveillance. Three patients (2.7%) in the SRS cohort and six (5.5%) in the active surveillance cohort exhibited neurological deterioration. One (0.9%) patient in the SRS-treated and 11 (10%) patients in the active surveillance cohort required surgical management of their meningioma during follow-up. CONCLUSIONS: SRS is associated with superior local control of asymptomatic, skull-based meningiomas as compared to active surveillance and does so with low morbidity rates. SRS should be offered as an alternative to active surveillance as the initial management of asymptomatic skull base meningiomas. Active surveillance policies do not currently specify the optimal time to intervention when meningioma growth is noted. Our results indicate that if active surveillance is the initial management of choice, SRS should be recommended when radiologic tumor progression is noted and prior to clinical progression.

Stereotactic radiosurgery for asymptomatic petroclival region meningiomas: a focused analysis from the IMPASSE study.

BACKGROUND: The optimal management of asymptomatic, petroclival meningiomas remains incompletely defined. The purpose of this study was to evaluate the safety and efficacy of upfront stereotactic radiosurgery (SRS) for patients with asymptomatic, petroclival region meningiomas. METHODS: This retrospective, international, multicenter study involved patients treated with SRS for an asymptomatic, petroclival region meningioma. Study endpoints included local tumor control rate, procedural complications, and the emergence of new neurological deficits. RESULTS: There were 72 patients (22 males, mean age 59.53 years (SD ± 11.9)) with an asymptomatic meningioma located in the petroclival region who were treated with upfront SRS. Mean margin dose and maximum dose were 13.26 (SD ± 2.72) Gy and 26.14 (SD ± 6.75) Gy respectively. Median radiological and clinical follow-up periods post-SRS were 52.5 (IQR 61.75) and 47.5 months (IQR 69.75) respectively. At last follow-up, tumor control was achieved in all patients. SRS-related complications occurred in 6 (8.33%) patients, with 3 of them (4.17%) exhibiting new neurological deficits. CONCLUSIONS: Upfront SRS for asymptomatic, petroclival region meningiomas affords excellent local tumor control and does so with a relatively low risk of SRS-related complications. SRS can be considered at diagnosis of an asymptomatic petroclival region meningioma. If active surveillance is initially chosen, SRS should be recommended when growth is noted during radiological follow-up.

Gamma Knife Radiosurgery of Distal Aneurysm: A Case Series.

A series of 3 patients (35-60 years old) with bleeding distal aneurysm not associated with AVM who underwent radiosurgery by gamma knife are reported. One isocentre centralized over the aneurysm was used; peripheral dose 24-28.8 Gy was applied. Control angiography 20-36 months after gamma knife surgery (GKS) demonstrated obliteration of both the aneurysm and the feeding artery, without deterioration of the neurological symptoms. Our case series implies that GKS might serve as a safe mini-invasive technique in the treatment of selected distal aneurysms.

Stereotactic radiosurgery for clinoid meningiomas: a multi-institutional study.

PURPOSE: Resection of clinoid meningiomas can be associated with significant morbidity. Experience with stereotactic radiosurgery (SRS) for clinoid meningiomas remains limited. We studied the safety and effectiveness of SRS for clinoid meningiomas. METHODS: From twelve institutions participating in the International Radiosurgery Research Foundation, we pooled patients treated with SRS for radiologically suspected or histologically confirmed WHO grade I clinoid meningiomas. RESULTS: Two hundred seven patients (median age: 56 years) underwent SRS for clinoid meningiomas. Median treatment volume was 8.02 cm3, and 87% of tumors were immediately adjacent to the optic apparatus. The median tumor prescription dose was 12 Gy, and the median maximal dose to the anterior optic apparatus was 8.5 Gy. During a median post-SRS imaging follow-up of 51.1 months, 7% of patients experienced tumor progression. Greater margin SRS dose (HR = 0.700, p = 0.007) and pre-SRS radiotherapy (HR = 0.004, p < 0.001) were independent predictors of better tumor control. During median visual follow-up of 48 months, visual function declined in 8% of patients. Pre-SRS visual deficit (HR = 2.938, p = 0.048) and maximal radiation dose to the optic apparatus of ≥ 10 Gy (HR = 11.297, p = 0.02) independently predicted greater risk of post-SRS visual decline. Four patients experienced new post-SRS cranial nerve V neuropathy. CONCLUSIONS: SRS allows durable control of clinoid meningiomas and visual preservation in the majority of patients. Greater radiosurgical prescription dose is associated with better tumor control. Radiation dose to the optic apparatus of ≥ 10 Gy and visual impairment before the SRS increase risk of visual deterioration.

Neuropsychological outcome in refractory obsessive-compulsive disorder treated with anterior capsulotomy including repeated surgery.

AIM: Anterior capsulotomy (AC) is one of the last therapeutic options for obsessive-compulsive disorder (OCD) refractory to conservative treatments. Several forms of cognitive dysfunction have been identified after assessment of neuropsychological outcomes in OCD patients; however, few studies focused on cognitive changes in OCD patients after surgery. In the present study, we evaluated the effects of AC on cognitive performance and mood status in patients with refractory OCD. METHODS: A total of 12 patients underwent bilateral AC between 2012 and 2019 at our institution. The patients (n = 12, female : male 5:7; mean age 39.7 years; duration ≥5 years) were assessed before and 6 months after intervention. The diagnosis of treatment-refractory OCD was based on recommended criteria for surgical treatment. Patients were assessed using a neuropsychological battery and questionnaires focused on anxiety-depressive symptomatology. The Yale-Brown Obsessive Compulsive Scale was administered as a measure of severity of OCD symptoms. RESULTS: We detected a significant decrease of OCD, and anxiety and depressive symptomatology assessed by Yale-Brown Obsessive Compulsive Scale, Beck Depression Inventory, and Beck Anxiety Inventory (P < 0.05) 6 months after AC in eight patients, and a partial decrease in four patients. Four patients underwent repeated AC with more pronounced improvement achieved after the first procedure. We did not detect decline in cognitive performance in any patients, but did find better visual memory performance (P < 0.05). CONCLUSION: AC reduced OCD and anxiety-depressive symptoms, and did not appear to influence cognitive performance, even after repeated surgery.

Combined treatment of a medulla oblongata hemangioblastoma via permanent cysto-cisternal drainage and (postponed) gamma knife radiosurgery: a case report and review of the literature.

BACKGROUND: Hemangioblastomas are histologically benign tumors with a variable degree of morbidity and mortality based on various factors, including their anatomical location. The following paper illustrates a unique approach of combined therapy of a brainstem hemangioblastoma (HB) not associated with von Hippel-Lindau disease (vHLd) located in the medulla oblongata. CASE DESCRIPTION: A 21-year-old preschool teacher presented with vertigo, followed by dysphagia, trouble coughing, tongue paresis and headache and vomiting. Magnetic resonance imaging (MRI) revealed a large cystic lesion with a small intramural nodule located in the left anterolateral medulla oblongata directly behind the vertebral artery. The diagnosis of hemangioblastoma was supported by digital subtraction angiography. CONCLUSION: Combined therapy consisted primarily of acute surgical fenestration and permanent drainage of the cystic portion of the tumor, due to symptomatic expansion. Follow-up stereotactic gamma knife radiosurgery was performed after 2 years for minor progression of the tumor nodule. To the best of our knowledge, this is the first time such approach has been described in the literature for this pathology.

Risk of radiation-associated intracranial malignancy after stereotactic radiosurgery: a retrospective, multicentre, cohort study.

BACKGROUND: A major concern of patients who have stereotactic radiosurgery is the long-term risk of having a secondary intracranial malignancy or, in the case of patients with benign tumours treated with the technique, the risk of malignant transformation. The incidence of stereotactic radiosurgery-associated intracranial malignancy remains unknown; therefore, our aim was to estimate it in a population-based study to assess the long-term safety of this technique. METHODS: We did a population-based, multicentre, cohort study at five international radiosurgery centres (Na Homolce Hospital, Prague, Czech Republic [n=2655 patients]; Ruber International Hospital, Madrid, Spain [n=1080], University of Pittsburgh Medical Center, Pittsburgh, PA, USA [n=1027]; University of Virginia, Charlottesville, VA, USA [n=80]; and NYU Langone Health System, New York, NY, USA [n=63]). Eligible patients were of any age, and had Gamma Knife radiosurgery for arteriovenous malformation, trigeminal neuralgia, or benign intracranial tumours, which included vestibular or other benign schwannomas, WHO grade 1 meningiomas, pituitary adenomas, and haemangioblastoma. Patients were excluded if they had previously had radiotherapy or did not have a minimum follow-up time of 5 years. The primary objective of the study was to estimate the incidence of stereotactic radiosurgery-associated intracranial malignancy, including malignant transformation of a benign lesion or development of radiation-associated secondary intracranial cancer, defined as within the 2 Gy isodose line. Estimates of age-adjusted incidence of primary CNS malignancies in the USA and European countries were retrieved from the Central Brain Tumor Registry of the United States (CBTRUS) and the International Agency for Research on Cancer (IARC) Global Cancer statistics. FINDINGS: Of 14 168 patients who had Gamma Knife stereotactic radiosurgery between Aug 14, 1987, and Dec 31, 2011, in the five contributing centres, 4905 patients were eligible for the analysis (had a minimum follow-up of 5 years and no history of previous radiation therapy). Diagnostic entities included vestibular schwannomas (1011 [20·6%] of 4905 patients), meningiomas (1490 [30·4%]), arteriovenous malformations (1089 [22·2%]), trigeminal neuralgia (565 [11·5%]), pituitary adenomas (641 [13·1%]), haemangioblastoma (29 [0·6%]), and other schwannomas (80 [1·6%]). With a median follow-up of 8·1 years (IQR 6·0-10·6), two (0·0006%) of 3251 patients with benign tumours were diagnosed with suspected malignant transformation and one (0·0002%) of 4905 patients was considered a case of radiosurgery-associated intracranial malignancy, resulting in an incidence of 6·87 per 100 000 patient-years (95% CI 1·15-22·71) for malignant transformation and 2·26 per 100 000 patient-years (0·11-11·17) for radiosurgery-associated intracranial malignancy. Two (0·0004%) of 4905 patients developed intracranial malignancies, which were judged unrelated to the radiation field. Overall incidence of radiosurgery-associated malignancy was 6·80 per 100 000 patients-years (95% CI 1·73-18·50), or a cumulative incidence of 0·00045% over 10 years (95% CI 0·00-0·0034). The overall incidence of 6·8 per 100 000, which includes institutions from Europe and the USA, after stereotactic radiosurgery was found to be similar to the risk of developing a malignant CNS tumour in the general population of the USA and some European countries as estimated by the CBTRUS and IARC data, respectively. INTERPRETATION: These data show that the estimated risk of an intracranial secondary malignancy or malignant transformation of a benign tumour in patients treated with stereotactic radiosurgery remains low at long-term follow-up, and is similar to the risk of the general population to have a primary CNS tumour. Although prospective cohort studies with longer follow-up are warranted to support the results of this study, the available evidence suggests the long-term safety of stereotactic radiosurgery and could support physicians counselling patients on Gamma Knife stereotactic radiosurgery. FUNDING: None.

Safety and efficacy of repeat radiosurgery for acromegaly: an International Multi-Institutional Study.

PURPOSE: Surgical resection is the first line treatment for growth hormone (GH) secreting tumors. Stereotactic radiosurgery (SRS) is recommended for patients who do not achieve endocrine remission after resection. The purpose of this study was to evaluate safety and efficacy of repeat radiosurgery for acromegaly. METHODS: Three hundred and ninety-eight patients with acromegaly treated with the Gamma Knife radiosurgery (Elekta AB, Stockholm) were identified from the International Gamma Knife Research Foundation database. Among these, 21 patients underwent repeated SRS with sufficient endocrine follow-up and 18 patients had sufficient imaging follow-up. Tumor control was defined as lack of adenoma progression on imaging. Endocrine remission was defined as a normal IGF-1 concentration while off medical therapy. RESULTS: Median time from initial SRS to repeat SRS was 5.0 years. The median imaging and endocrine follow-up duration after repeat SRS was 3.4 and 3.8 years, respectively. The median initial marginal dose was 17 Gy, and the median repeat marginal dose was 23 Gy. Of the 18 patients with adequate imaging follow up, 15 (83.3%) patients had tumor control and of 21 patients with endocrine follow-up, 9 (42.9%) patients had endocrine remission at last follow-up visit. Four patients (19.0%) developed new deficits after repeat radiosurgery. Of these, 3 patients had neurologic deficits and 1 patient had endocrine deficit. CONCLUSIONS: Repeat radiosurgery for persistent acromegaly offers a reasonable benefit to risk profile for this challenging patient cohort. Further studies are needed to identify patients best suited for this type of approach.

Role of gamma knife radiosurgery in the treatment of prolactinomas.

PURPOSE: Stereotactic radiosurgery is one of the treatment options for prolactinomas, the most commonly used being Gamma Knife Radiosurgery (GKRS). GKRS is indicated mainly in the treatment of dopamine agonist (DA)-resistant prolactinomas. In our study, we report on our experience in treating prolactinoma patients by GKRS. METHODS: Twenty-eight patients were followed-up after GKRS for 26-195 months (median 140 months). Prior to GKRS, patients were treated with DAs and 9 of them (32.1%) underwent previous neurosurgery. Cavernous sinus invasion was present in 16 (57.1%) patients. Indications for GKRS were (i) resistance to DA treatment (17 patients), (ii) drug intolerance (5 patients), or (iii) attempts to reduce the dosage and/or shorten the length of DA treatment (6 patients). RESULTS: After GKRS, normoprolactinaemia was achieved in 82.1% of patients, out of which hormonal remission (normoprolactinaemia after discontinuation of DAs) was achieved in 13 (46.4%), and hormonal control (normoprolactinaemia while taking DAs) in 10 (35.7%) patients. GKRS arrested adenoma growth or decreased adenoma size in all cases. Two patients (8.3%) developed hypopituitarism after GKRS. Prolactinoma cystic transformation with expansive behaviour, manifested by bilateral hemianopsia, was observed in one patient. CONCLUSIONS: GKRS represents an effective treatment option, particularly for DA-resistant prolactinomas. Normoprolactinaemia was achieved in the majority of patients, either after discontinuation of, or while continuing to take, DAs. Tumour growth was arrested in all cases. The risk of the development of hypopituitarism can be limited if the safe dose to the pituitary and infundibulum is maintained.

Repeat stereotactic radiosurgery for Cushing's disease: outcomes of an international, multicenter study.

Stereotactic radiosurgery (SRS) is frequently used for Cushing's disease (CD) after failed pituitary surgery. Management of patients with persistent CD after failed SRS is complex, as the alternative therapeutic options harbor significant risks. The outcomes of repeat pituitary radiosurgery, however, have not been described. We sought to determine the outcomes of repeat SRS in patients with CD. We pooled data from five institutions participating in the International Gamma Knife Research Foundation for patients with recurrent or persistent CD ≥ 12 months after initial SRS. Patients were included in the study if they had ≥ 6 months endocrine follow-up after repeat SRS. Twenty patients were included in the study. Repeat single-session SRS was performed 1.3-9.7 years after initial SRS. Median endocrine follow-up was 6.6 years (1.4-19.1 years). Median margin dose was 20 Gy (range 10.8-35 Gy). Endocrine remission after second SRS was noted in 12 patients (60%), with a median time to remission of 6 months (range 2-64 months). Biochemical recurrence occurred in two patients (17%) after initial remission. Overall, the cumulative rates of durable endocrine remission at 5 and 10 years were 47 and 53%, respectively. Two patients (10%) experienced adverse radiation effects, including transient visual loss and permanent diplopia. Repeat SRS achieves lasting biochemical remission in approximately half of patients with CD refractory to both prior microsurgery and SRS. Because of the morbidity of refractory or recurrent CD, repeat SRS should be considered for carefully selected patients with hypercortisolism confirmed one or more years after initial SRS.

Gamma knife radiosurgery for local recurrence of glioblastoma.

OBJECTIVE: Local recurrence of glioblastoma is observed in most patients after standard oncologic treatment (surgery, chemotherapy and radiotherapy). Stereotactic radiosurgery with the Leksell Gamma Knife (SRS with LGK) was used to treat recurrent tumors in selected cases, and retrospective analysis of treatment outcome was performed. METHODS: Altogether 126 patients were treated for glioblastoma at our center from 1992-2014. Sixty-nine patients (55%) were male and 57 (45%) female, with a median age of 56 years (range 17-80 years). Prior to LGK radiosurgery, 123 (98%) underwent surgery, 126 (100%) radiotherapy and 116 (92%) chemotherapy. The median Karnofsky score before LGK radiosurgery was 90% (range 50-100), and the median time from GBM diagnosis to LGK radiosurgery was 12 months (range 1-96 months). The median tumor volume was 3.75 cm3 (range 0.04-37.10 cm3). LGK radiosurgery was performed in a single fraction with a median minimal tumor dose of 12 Gy (range 10-25 Gy) on a median 50% (range 40-86%) isodose line. Two and more LGK radiosurgeries were performed in 19 (15%) cases, a median interval of 9.6 months (range 2-45 months) from the initial LGK radiosurgery. The median prescribed dose in these patients was 12.6 Gy (range 10-15 Gy), and the median volume 5.8 cm3 (range 0.1-13.7 cm3). RESULTS: The median survival from GBM diagnosis was 20 months (range 6-237 months). The median survival after LGK radiosurgery was 7 months (range 1-223 months). The one year survival after LGK radiosurgery was 27%, 2 years 8%, and more than 3 years 4%. Tumor regression on MR images was observed in 17% of patients at a median interval of 7 months. The median interval to tumor progression on MR images after LGK treatment was 8.5 months. No treatment-related radionecrosis with expansive behaviour was detected after radiosurgery. CONCLUSION: We show that LGK radiosurgery is a safe palliative treatment modality in patients with recurrent GBM.

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.

Late morphological changes after radiosurgery of brain arteriovenous malformations: an MRI study.

BACKGROUND: Radiosurgery by Gamma Knife (GK) is an effective treatment for brain arteriovenous malformations (AVM). The aim of the present study was to evaluate late, radiation-induced changes detectable by MRI after AVM radiosurgery in patients treated minimally 10 years prior, with AVM obliteration proven by angiography. METHODS: Thirty-five patients with 37 AVMs were included. AVMs were irradiated 16.6 ± 3.5 years prior with AVM obliteration proven 13 ± 4 years prior. All patients underwent recent MRI examinations, including application of gadolinium-based contrast. RESULTS: In one case, post-irradiative cystic formation with mass effect and signs of hemorrhage requiring surgery was found. Post-gadolinium enhancement at the site of obliterated nidi was apparent in 28 of 37 cases (76 %). In all cases except one, the mean volume of enhancement at the time of review was clearly lower than the volume of the originally irradiated AVM (88 ± 20 %; median 92 %); in one case the extent was 142 % greater than the irradiated AVM. When we compared enhancing and non-enhancing nidi, we found that enhancing nidi were significantly larger than non-enhancing nidi at the time of radiosurgery (4.39 ± 3.35 cc vs. 0.89 ± 0.79 cc, p = 0.004). Enhancement was not influenced by total radiation dose, patient age at the time of irradiation, duration since radiosurgery, or the number of irradiations. Wallerian degeneration was found in nine of 37 cases (24 %); in six cases the optical tracts were affected and visual field defects were proven. In five of nine cases (55.6 %) with Wallerian degeneration previous hemorrhage was present. Dual vascular pathology was found in eight of 35 patients (23 %). CONCLUSIONS: GK radiosurgery for AVM is a safe treatment method although delayed complications may occur. Post-gadolinium enhancement of obliterated nidi may indicate an active post-irradiative process.

Gamma knife radiosurgery for Cushing's disease and Nelson's syndrome.

PURPOSE: This paper presents our 18 years of experience in treating ACTH secreting adenomas (Cushing's disease and Nelson's syndrome) using the Leksell gamma knife (LGK) irradiation. METHODS: Twenty-six patients with Cushing's disease were followed-up after LGK irradiation for 48-216 months (median 78 months). Seventeen patients had undergone previous surgery, in nine patients LGK irradiation was the primary therapy. Furthermore, 14 patients with Nelson's syndrome were followed-up for 30-204 months (median 144 months). RESULTS: LGK treatment resulted in hormonal normalization in 80.7 % of patients with Cushing's disease. Time to normalization was 6-54 months (median 30 months). The volume of the adenoma decreased in 92.3% (in 30.7% disappeared completely). There was no recurrence of the disease. In all 14 patients with Nelson's syndrome ACTH levels decreased (in two patients fully normalized) their ACTH levels. When checked up 5-10 years after irradiation regrowth of the adenoma was only detected in one patient (9.1%), in 27.3% adenoma volume remained unchanged, in 45.4% adenoma volume decreased and in 18.2% adenoma completely disappeared. Hypopituitarism did not develop in any patient where the critical dose to the pituitary and distal infundibulum was respected. CONCLUSION: LGK radiation represents an effective and well-tolerated option for the treatment of patients with Cushing's disease after unsuccessful surgery and may be valuable even as a primary treatment in patients who are not suitable for, or refuse, surgery. In the case of Nelson's syndrome it is possible to impede tumorous growth and control the size of the adenoma in almost all patients.

Radiosurgery for Large Arteriovenous Malformations as a Single-Session or Staged Treatment.

BACKGROUND/OBJECTIVES: The treatment of large arteriovenous malformations (AVMs) presents a challenge and the effectiveness of radiosurgery decreases with increasing treatment volume. Here, we analyzed and compared single-session treatment for AVMs >15 cm3 with staged treatment, when the volume of a large AVM was divided into 2 or more compartments, which were subsequently treated at intervals of a few months. In the event that complete obliteration was not achieved within 3 years, repeat radiosurgery was considered. METHODS/RESULTS: Between 1993 and 2011, gamma-knife radiosurgery was performed on 50 patients with large AVMs. A total of 27 of them, with volumes ranging from 15.1 to 27 cm3 (median = 17.8), were treated in a single session, with a marginal dose ranging from 10 to 17 Gy (median = 15). Complete obliteration was achieved in 7 (26%) of these; in 14 patients the treatment was repeated after a median of 38 months. The volume of AVMs subjected to repeat treatment regressed and ranged from 6.76 to 16.4 cm3 (median = 7.7), with the marginal dose ranging from 13 to 18 Gy (median = 17); 10 patients later achieved complete obliteration at a median of 79 months after the initial treatment. Overall, 63% of patients achieved complete obliteration of AVM after treatment. Rebleeding in a latent period was recorded in 3 patients (11%) and symptomatic collateral edema in 2 (7%); 23 patients were treated using the staged method, with the interval between staged treatments usually being 6 months. Their overall AVM volume ranged from 13.2 to 46.6 cm3 (median = 23.3), the volume for a single stage ranged from 4.5 to 31.3 cm3 (median 11.7), and the marginal dose ranged from 10 to 18 Gy (median = 17). Complete obliteration was achieved in 4 (17%) of them, in 8 patients the treatment was repeated at a median of 53 months after the first treatment, and a third retreatment was performed on 2 patients 98 and 102 months, respectively, after the first treatment. The volume for repeated treatment of AVMs ranged from 0.81 to 7.7 cm3 (median = 3.3), with the marginal dose ranging from 14 to 20 Gy (median 17.5). Of all the retreated patients, 5 AVMs subsequently achieved complete obliteration. Overall, 9 patients (39%) were totally cured. Rebleeding in a latent period was observed in 1 of these patients (4.3%) and symptomatic edema in another 1 (4.3%). CONCLUSIONS: Radiosurgery of large AVMs is a valuable treatment either as a single-session or staged treatment, with a reasonable chance of cure and a low risk of complications.

Morphological changes after radiosurgery for mesial temporal lobe epilepsy.

BACKGROUND: To review our experience with morphological developments during the long-term follow-up of patients treated by Gamma Knife radiosurgery for mesial temporal lobe epilepsy. METHOD: Between 1995 and 1999, we treated 14 patients with marginal doses of 24 Gy (n = 6) and 18-20 Gy (n = 8). Nine of these were operated on for insufficient seizure control. We reviewed seizure outcome and magnetic resonance images in both operated and unoperated patients and also re-examined histopathology specimens. RESULTS: Of the nine operated patients, two were Engel IIIA, one was IVA, five were IVB, and one was Engel IVC prior to surgery. At their final visit, five cases had become Engel class IA, one patient was ID, and two were IIC. In one patient the follow-up was not long enough for classification. Of the five unoperated patients, one was Engel class IB, one was IIIA, one IIB and one IVB at their final visit. Radionecrosis developed in 11 patients, occurring more often and earlier in those treated with higher doses. Collateral edema reached outside the temporal lobe in six patients, caused uncal herniation in two and intracranial hypertension in three. During longer follow-up, postnecrotic pseudocysts developed in 9 patients, and postcontrast enhancement persisted for 2.5-16 years after GKRS in all 14 patients. In five of them we detected its progression between 2 and 16 years after treatment. Signs of neoangiogenesis were found in two patients and microbleeds could be seen in five. Histopathology revealed blood vessel proliferation and macrophage infiltration. CONCLUSIONS: Early delayed complications and morphological signs suggesting a risk of development of late delayed complications are frequent after radiosurgery for mesial temporal lobe epilepsy. Together with its unproven antiseizure efficacy, these issues should be taken into account when planning future studies of this method.