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OBJECTIVE Resection of meningiomas in direct contact with the anterior optic apparatus carries risk of injury to the visual pathway. Stereotactic radiosurgery (SRS) offers a minimally invasive alternative. However, its use is limited owing to the risk of radiation-induced optic neuropathy. Few SRS studies have specifically assessed the risks and benefits of treating meningiomas in direct contact with the optic nerve, chiasm, or optic tract. The authors hypothesized that SRS is safe for select patients with meningiomas in direct contact with the anterior optic apparatus. METHODS The authors performed an international multicenter retrospective analysis of 328 patients across 11 institutions. All patients had meningiomas in direct contract with the optic apparatus. Patients were followed for a median duration of 56 months after SRS. Neurological examinations, including visual function evaluations, were performed at follow-up visits. Clinical and treatment variables were collected at each site according to protocol. Tumor volumes were assessed with serial MR imaging. Variables predictive of visual deficit were identified using univariable and multivariable logistic regression. RESULTS SRS was the initial treatment modality for 64.6% of patients, and 93% of patients received SRS as a single fraction. Visual information was available for 302 patients. Of these patients, visual decline occurred in 29 patients (9.6%), of whom 12 (41.4%) had evidence of tumor progression. Visual decline in the remaining 17 patients (5.6%) was not associated with tumor progression. Pre-SRS Karnofsky Performance Status predicted visual decline in adjusted analysis (adjusted OR 0.9, 95% CI 0.9–1.0, p < 0.01). Follow-up imaging data were available for 322 patients. Of these patients, 294 patients (91.3%) had radiographic evidence of stability or tumor regression at last follow up. Symptom duration was associated with tumor progression in adjusted analysis (adjusted OR 1.01, adjusted 95% CI 1.0–1.02, adjusted p = 0.02). CONCLUSIONS In this international multicenter study, the vast majority of patients exhibited tumor control and preservation of visual function when SRS was used to treat meningioma in direct contact with the anterior optic pathways. SRS is a relatively safe treatment modality for select patients with perioptic meningiomas in direct contact with the optic apparatus.

OBJECTIVE Stereotactic radiosurgery (SRS) provides a safe and effective therapeutic modality for patients with pituitary adenomas. The mechanism of delayed endocrine deficits based on targeted radiation to the hypothalamic-pituitary axis remains unclear. Radiation to normal neuroendocrine structures likely plays a role in delayed hypopituitarism after SRS. In this multicenter study by the International Radiosurgery Research Foundation (IRRF), the authors aimed to evaluate radiation tolerance of structures surrounding pituitary adenomas and identify predictors of delayed hypopituitarism after SRS for these tumors. METHODS This is a retrospective review of patients with pituitary adenomas who underwent single-fraction SRS from 1997 to 2019 at 16 institutions within the IRRF. Dosimetric point measurements of 14 predefined neuroanatomical structures along the hypothalamus, pituitary stalk, and normal pituitary gland were made. Statistical analyses were performed to determine the impact of doses to critical structures on clinical, radiographic, and endocrine outcomes. RESULTS The study cohort comprised 521 pituitary adenomas treated with SRS. Tumor control was achieved in 93.9% of patients over a median follow-up period of 60.1 months, and 22.5% of patients developed new loss of pituitary function with a median treatment volume of 3.2 cm3. Median maximal radiosurgical doses to the hypothalamus, pituitary stalk, and normal pituitary gland were 1.4, 7.2, and 11.3 Gy, respectively. Nonfunctioning adenoma status, younger age, higher margin dose, and higher doses to the pituitary stalk and normal pituitary gland were independent predictors of new or worsening hypopituitarism. Neither the dose to the hypothalamus nor the ratio between doses to the pituitary stalk and gland were significant predictors. The threshold of the median dose to the pituitary stalk for new endocrinopathy was 10.7 Gy in a single fraction (OR 1.77, 95% CI 1.17–2.68, p = 0.006). CONCLUSIONS SRS for the treatment of pituitary adenomas affords a high tumor control rate with an acceptable risk of new or worsening endocrinopathy. This evaluation of point dosimetry to adjacent neuroanatomical structures revealed that doses to the pituitary stalk, with a threshold of 10.7 Gy, and doses to the normal gland significantly increased the risk of post-SRS hypopituitarism. In patients with preserved pre-SRS neuroendocrine function, limiting the dose to the pituitary stalk and gland while still delivering an optimal dose to the tumor appears prudent.

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. 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. 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

Objective Trigeminal neuralgia (TN) in patients with multiple sclerosis (MS) is a challenging condition to manage that is treated with Gamma Knife radiosurgery (GKRS). The aim of this report is to assess the safety, efficacy, and durability of GKRS for the treatment of TN in patients with MS. Our findings are compared with those of the existing literature and discussed. Methods We retrospectively reviewed all patients at our institution who underwent GKRS for the treatment of TN secondary to MS and had 1 or more years of follow-up. Preoperative and postoperative pain intensities and facial numbness were evaluated with the Barrow Neurological Institute scores. Durability of successful pain relief was statistically evaluated with Kaplan–Meier analysis. The prognostic role of perioperative factors was investigated and analyzed using Cox proportional hazards regression. Results There were 29 patients with MS-TN who underwent GKRS at our institution. Two patients underwent bilateral treatment. Four patients underwent repeat GKRS for pain recurrence. The median period of follow-up assessment was 33 months. Rates of reasonable pain reduction at 1, 3, and 5 years were 70%, 57%, and 57% respectively. All patients who underwent repeat GKRS had durable pain reduction. No prognostic factor for successful pain reduction was found. Conclusions Our study shows that GKRS for the treatment of TN secondary to MS is a safe and effective procedure in controlling pain in the short term but often fails to provide long-term pain control. GKRS can be safely repeated to prolong the time of pain reduction.

OBJECTIVENelson’s syndrome is a rare and challenging neuroendocrine disorder, and it is associated with elevated adrenocorticotrophic hormone (ACTH) level, skin hyperpigmentation, and pituitary adenoma growth. Management options including resection and medical therapy are traditional approaches. Ionizing radiation in the form of Gamma Knife radiosurgery (GKRS) is also being utilized to treat Nelson’s syndrome. In the current study the authors sought to better define the therapeutic role of stereotactic radiosurgery (SRS) in Nelson’s syndrome.METHODSStudy patients with Nelson’s syndrome were treated with single-fraction GKRS (median margin dose of 25 Gy) at 6 different centers as part of an International Radiosurgery Research Foundation (IRRF) investigation. Data including neurological function, endocrine response, and radiological tumor response were collected and sent to the study-coordinating center for review. Fifty-one patients with median endocrine and radiological follow-ups of 91 and 80.5 months from GKRS, respectively, were analyzed for endocrine remission, tumor control, and neurological outcome. Statistical methods were used to identify prognostic factors for these endpoints.RESULTSAt last follow-up, radiological tumor control was achieved in 92.15% of patients. Endocrine remission off medical management and reduction in pre-SRS ACTH level were achieved in 29.4% and 62.7% of patients, respectively. Improved remission rates were associated with a shorter time interval between resection and GKRS (p = 0.039). Hypopituitarism was seen in 21.6% and new visual deficits were demonstrated in 15.7% of patients.CONCLUSIONSGKRS affords a high rate of pituitary adenoma control and improvement in ACTH level for the majority of Nelson’s syndrome patients. Hypopituitarism is the most common adverse effect from GKRS in Nelson’s syndrome patients and warrants longitudinal follow-up for detection and endocrine replacement.

Medial thalamotomy using stereotactic radiosurgery (SRS) is a potential treatment for intractable pain. However, the ideal treatment parameters and expected outcomes from this procedure remain unclear. The aim of this systematic review is to provide further insights on medial thalamotomy using SRS, specifically for intractable pain. A systematic review was performed to identify all clinical articles discussing medial thalamotomy using SRS for intractable pain. Only studies in which SRS was used to target the medial thalamus for pain were included. For centers with multiple publications, care was taken to avoid recounting individual patients. The literature review revealed six studies describing outcomes of medial thalamotomy using SRS for a total of 125 patients (118 included in the outcome analysis). Fifty-two patients were treated for cancer pain across three studies, whereas five studies included 73 patients who were treated for nonmalignant pain. The individual studies demonstrated initial meaningful pain reduction in 43.3-100% of patients, with an aggregate initial meaningful pain reduction in 65 patients (55%) following SRS medial thalamotomy. This effect persisted in 45 patients (38%) at the last follow-up. Adverse events were observed in six patients (5%), which were related to radiation in five patients (4%). Medial thalamotomy using SRS is effective for select patients with treatment-resistant pain and is remarkably safe when modern radiation delivery platforms are used. More posteriorly placed lesions within the medial thalamus were associated with better pain relief. More studies are warranted to shed light on differences in patient responses.

PURPOSE/OBJECTIVE(S) Multiple single institution retrospective studies have suggested that managing melanoma brain metastases (MBM) with stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICI) is associated with improved overall survival (OS) when administered concurrently (within 4 weeks) rather than sequentially (ICI and SRS administered more than 4 weeks apart). However, there is a paucity of data quantifying the risk of developing radiation necrosis (RN) in this setting. MATERIALS/METHODS The International Radiosurgery Research Foundation approved the analysis. The Kaplan Meier method and log-rank test were used to compare OS and local control (LC) at 1- and 2-years post SRS. Factors associated with the development of RN and OS were further analyzed using logistic and Cox proportional hazards regression models. The null hypothesis was rejected for P < 0.05. RESULTS There were 254 patients with 1,322 MBM treated across 10 international institutions. The median follow-up was 12.9 months, median age was 63 years (interquartile range [IQR]: 51-73 years), BRAF mutation was present in 46.6% of patients, active extracranial disease was present in 70% of patients, and the median Karnofsky Performance Status (KPS) was 90. SRS/ICI was administered concurrently in 46.5% of patients. All patients were treated on the stereotactic radiosurgery platform. The median margin dose was 20 Gy (IQR: 18-21 Gy), median number of fractions was 1 (range: 1-4), mean total brain metastasis volume was 3.4 cc and the mean V12 Gy was 8.7 cc. Radiation necrosis occurred in 14.2% of patients (5.9% Grade 1; 5.1% Grade 2; 2.8% Grade 3; 0.4% Grade 4). Overall survival at 1-year was 77.4% vs. 72.1%, and at 2-years was 63.1% vs. 46.1% (P = 0.048) for concurrent and sequential therapy, respectively. Local control at 1-year was 91.5% vs. 84.6%, and at 2-years was 84.9% vs. 75.6% (P = 0.12) for concurrent and sequential therapy, respectively. On multivariate logistic regression total treated brain metastasis volume (odds radio [OR]: 1.11; 95% confidence interval [CI]: 1.03-1.20; P = 0.008) was associated with a higher risk of development of RN; however, sequential therapy (OR: 0.97; 95% CI: 0.46-2.06; P = 0.94), and V12 (OR: 0.98; 95% CI: 0.95-1.01; P = 0.22) were not statistically significant. On multivariate cox regression, sequential therapy (hazard ratio [HR]: 1.58; 95% CI: 1.05-2.42; P = 0.03) and KPS (HR: 0.96; 95% CI: 0.94-0.98; P < 0.001) were prognostic factors for OS, while the presence of extracranial disease (HR: 1.03; 95% CI: 0.66-1.59; P = 0.90) and age (HR: 1.01; 95% CI: 1.00-1.02; P = 0.25) were not prognostic. CONCLUSION In appropriately selected patients with MBM, concurrent administration of SRS/ICI may be associated with improved OS without an increased risk of RN when compared to sequential therapy. The risk of RN appears to increase with irradiated brain volume; therefore, hypofractionated SRS may be considered in patients with high volume disease. Prospective data are needed to further evaluate these findings. AUTHOR DISCLOSURE E.J. Lehrer: None. J. Gurewitz: None. T.D. Malouff: ASTRO Bylaws Committee. K. Bernstein: None. D. Kondziolka: None. P. Bonney: None. S.I. Patel: Independent Contractor; Alberta Health Services. Research Grant; Alberta Cancer Foundation. Travel Expenses; University Hospital Foundation. Chair; Alberta Health Services. Co-Director; Alberta Health Services. Manage and screen wish applications; Make-A-Wish Foundation (Northern Alberta Chapter). J.D. Palmer: Research Grant; Varian Medical Systems, The Kroger Company. Consultant; Huron Consulting. Speaker's Bureau; Varian Medical Systems, Depuy Synthes. Advisory Board; Novocure. Member of panel; NCCN.K. Fakhoury: None. C.G. Rusthoven: Employee; SURVIVEiT (nonprofit cancer patient advocacy). Research Grant; Takeda. Advise regarding patient-facing medical content; SURVIVEiT.D. Mathieu: None. C. Deibert: None. P. Picozzi: None. B. Jones: None. C. Lee: None. S. Sharma: None. A. Niranjan: None. J.P. Sheehan: Neuropoint Alliance. M. Ahluwalia: None. D.M. Trifiletti: None.

Perioptic meningiomas, defined as those in contact or adjacent (within a 2 or 3 mm distance) to the anterior optic pathways (AOP, optic nerves, and chiasm), are challenging lesions to manage with radiation ablative therapies due to the vicinity to the radiation-sensible optic apparatus. Because of the perceived risk of damaging the AOP with single-session stereotactic radiosurgery, hypofractionated radiation delivery regimens have been introduced since the last two decades. Hypofractionated radiosurgery involves the delivery of an ablative radiation dose in 2–5 large fractions at 24- or 12-h intervals and allows the surgeon to combine the high conformality and targeting accuracy of SRS platforms with the radiobiological advantages of dose fractionation. Various studies have investigated the safety and efficacy of hypofractionated radiosurgery for the treatment of perioptic meningiomas using the Gamma Knife, the CyberKnife, and linear accelerators. Overall, those studies have confirmed that hypofractionated stereotactic radiosurgery is effective in controlling the growth of perioptic meningiomas and is safe to the anterior optic pathways, though follow-up assessment periods and number of patients included remain limited. The aim of this chapter is to review the literature about stereotactic hypofractionated radiosurgery for the treatment of perioptic meningiomas. These outcomes are compared with those of alternative therapies including conventionally fractionated radiation therapy and single-session radiosurgery. Finally, the radiation tolerance of the optic pathways when using the different radiation delivery regimens is discussed.

Background Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is a primary headache syndrome with an unclear pathogenesis, and only in very few cases, SUNCT is secondary to known lesions (secondary SUNCT). Several pharmacological as well as interventional and invasive treatments have been used to treat SUNT cases, with no definitive results. We describe a patient with idiopathic SUNCT syndrome, successfully treated with gamma knife radiosurgery and we report a review of the cases of the literature treated with radiosurgery. Case Report A 63-year-old woman complained of episodes of intense and regular paroxysmal facial pain in the territory of the maxillary branch of the trigeminal nerve accompanied by inflammation of conjunctiva and involuntary lacrimation from 2006. During the following years, she received several treatments: combination of drugs, acupuncture, and endonasal infiltration of the sphenopalatine ganglion. The frequency of the painful attacks increased progressively and it was impossible for her to have a normal active life. Combined gamma knife radiosurgery treatment, targeting the trigeminal nerve (80 Gy maximum dose) and the sphenopalatine ganglion (80 Gy maximum dose) was performed in April 2016 (visual analog score before treatment = 6). Pain gradually reduced in the following months, as well as frequency and severity of the attacks. No sensory deficit developed. The follow-up length of our patient is 37 months: she is nearly pain free (visual analog score = 2) and has resumed a normal life. Conclusions Patients with idiopathic SUNCT have few therapeutic options. Our case demonstrates that gamma knife radiosurgery is a feasible and effective noninvasive option to treat patients with medically refractory idiopathic SUNCT.

Background Metastatic meningiomas (MMs) are rare (0.1 of 100 cases). Their treatment requires a multimodal approach, with surgery, radiotherapy, chemotherapy, and radiosurgery, which allows a long-term local control (LC) and an extension of free survival. In this study, the authors performed a review of the literature and reported 2 cases of patients affected by extracranial MMs, with long-term follow-up. Case Description Case 1: A 48-year-old woman was admitted for resection of an extra-axial falx lesion (meningioma G1). After 2 years, the lesion got a local recurrence, resected with a histologic diagnosis of meningioma G3. During the next 9 years, the patient underwent 5 Gamma Knife radiosurgery (GKRS) procedures for local recurrence. At 56 years, she was readmitted for a surgical local recurrence (histologic definition: anaplastic meningioma G3). At the age of 62, the patient underwent a right lobectomy for a lung mass (histologic diagnosis: anaplastic meningioma G3). After that, multiple lesions at soma L5 and adrenal gland were discovered and then monitored. Case 2: A 48-year-old woman was operated for a lesion involving torcular herophili (meningioma G2). After 3 years, a local recurrence requires GKRS combined with tamoxifen. In the next 7 years, she underwent 5 GKRS procedures for local recurrence. The patient also underwent chemotherapy with octreotide. At the age of 61, she discovered multiple lesions in both lungs, liver, and kidney. A hepatic biopsy showed anaplastic meningioma G3. Also this patient does not suffer from any neurologic or clinical deficits. Conclusions LC in malignant meningioma is achievable through a multimodal approach; GKRS makes possible LC, but a novel aspect of these lesions is opened to discussion: the metastases. These reports show that multimodal treatment for MMs is an effective approach with good LC and improvement of overall survival. However, a long survival may allow systemic diffusion of the disease, in particular, when sagittal sinus is involved.

BACKGROUND: The specificity of imaging alone in diagnosing posterior fossa lesions is insufficient, hence the importance of biopsy for diagnostic, therapeutic and prognostic purposes. Concerning the operative technique, many studies have demonstrated the superior safety of stereotactic biopsy over craniotomy and superior accuracy of frame-based systems over frameless ones as far as the posterior fossa is concerned; however versatile, frame-based instruments bear some intrinsic limitations in the positioning of frame in lower lesions mainly in short neck and kyphotic patients. For all these reasons, a more proficient technical bioptic approach to the posterior fossa and lower brainstem is sometimes required. METHODS: In order to obtain a specimen a Leksell System (Elekta ® ) constituted by the Leksell Coordinate G Frame (Article No: 014611), 4 adjustable posts (Article No: 1006476), 4 reusable screws (Article No: 1006581), an open indicator box (Article No: 1006559), a Leksell Multipurpose Stereotactic Arc (Article No: 1008174) and a Sedan Needle (Article No: A2430-01) are required. RESULTS: This is a simple and reliable technique to obtain a brainstem/cerebellar specimen maintaining unchanged the know risks of the procedure, as well the morbidity and mortality. We otherwise recommend this procedure to be performed by a team of neurosurgeons trained in stereotaxy. CONCLUSIONS: If meticulously planned, our modified procedure provide a direct and precise access to deep seated areas of the posterior fossa and brainstem and is particularly helpful in those patients with short neck and kyphosis in which is crucial obtain an istopathologic diagnosis in lower posterior fossa.

Purpose Our aim was to prospectively analyze the use of contrast-enhanced ultrasound (CEUS) in the quantitative assessment of the response of uveal melanoma (UM) to gamma-knife radiosurgery (GKR), investigating whether changes in tumor vascularization precede thickness reduction, which on average occurs at 12 months after GKR. Methods Ten patients with UM treated with GKR underwent sonography (US) and CEUS at baseline and at 3, 6, and 12 months after GKR. The transverse diameter, thickness, and quantitative parameters of the UM (ie, area under the curve in the wash-in phase, wash-in perfusion index, peak enhancement, and wash-in rate) were calculated by using dedicated software and compared by using Wilcoxon's signed-rank test. Results The mean tumor thickness on US was significantly less at both 6 (6.6 mm) and 12 months after GKR (5.8 mm) than it was at baseline (8.3 mm; p

ObjectSince the 1990s, Gamma Knife radiosurgery (GKRS) has become the first-line treatment option for small- to medium-size vestibular schwannomas (VSs), especially in patients without mass effect–related symptoms and with functional hearing. The aim of this study was to assess the safety and efficacy of GKRS, in terms of tumor control, hearing preservation, and complications, in a series of 379 consecutive patients treated for VS.MethodsOf 523 patients treated at the authors' institution for VS between 2001 and 2010, the authors included 379 who underwent GKRS as the primary treatment. These patients were not affected by Type 2 neurofibromatosis and had clinical follow-up of at least 36 months. Clinical follow-up (mean and median 75.7 and 69.5 months, respectively) was performed for all patients, whereas audiometric and quantitative radiological follow-up examinations were obtained for only 153 and 219 patients, respectively. The patients' ages ranged from 23 to 85 years (mean 59 years). The mean tumor volume was 1.94 ± 2.2 cm3 (median 1.2 cm3, range 0.013–14.3 cm3), and the median margin dose was 13 Gy (range 11–15 Gy). Parameters considered as determinants of the clinical outcome were long-term tumor control, hearing preservation, and complications. A statistical analysis was performed to correlate clinical outcomes with the radiological features of the tumor, dose-planning parameters, and patient characteristics.ResultsControl of the tumor with GKRS was achieved in 97.1% of the patients. In 82.7% of the patients, the tumor volume had decreased at the last follow-up, with a mean relative reduction of 34.1%. The rate of complications was very low, with most consisting of a transient worsening of preexisting symptoms. Patients who had vertigo, balance disorders, or facial or trigeminal impairment usually experienced a complete or at least significant symptom relief after treatment. However, no significant improvement was observed in patients previously reporting tinnitus. The overall rate of preservation of functional hearing at the long-term follow-up was 49%; in patients with hearing classified as Gardner-Robertson (GR) Class I, this value was 71% and reached 93% among cases of GR Class I hearing in patients younger than 55 years.ConclusionsGamma Knife radiosurgery is a safe and effective treatment for VS, achieving tumor control in 97.1% of cases and resulting in a very low morbidity rate. Younger GR Class I patients had a significantly higher probability of retaining functional hearing even at the 10-year follow-up; for this reason, the time between symptom onset, diagnosis, and treatment should be shortened to achieve better outcomes in functional hearing preservation.

AimsThe aim of the present work is to assess the main predictors of the most clinically relevant radio-induced effects after Gamma Knife stereotactic radiosurgery (GKRS) for uveal melanoma (UM).Materials and methodsMedical records and three-dimensional dosimetry data of critical structures of 66 patients were retrospectively reviewed. Cox’s proportional hazard model was used to identify clinical and dosimetric variables as independent risk factor for GKRS-related complications.ResultsThe fraction of the posterior segment receiving more than 20Gy (V20), Bruch’s membrane rupture and tumour thickness were significant prognostic factors for neovascular glaucoma. A clear relationship with the dose received by 1% of the optic nerve (D1%) was found for radiation retinopathy and papillopathy. Multivariables models resulted for visual acuity (VA) reduction >20% of the basal value and for complete VA loss, both including largest tumour diameter and D1% to the optic nerve. The predictive model for complete VA loss includes also Bruch’s membrane rupture. An alternative model for complete visual acuity loss, including the optic nerve-prescription isodose minimum distance, was also suggested.ConclusionsWe found clinical and dosimetric variables to clearly predict the risk of the main side effects after GKRS for UM. These results may provide dose constraints to critical structures, potentially able to reduce side effects. Constraining D1% to the optic nerve below 12-13Gy may result in a dramatic reduction of blindness risk, while reducing V20 of the posterior segment of the bulb could limit the neovascular glaucoma onset.

"Background: The reported AVMs obliteration rate after Gamma Knife radiosurgery (GKS) ranges from 70 to 94 %. The objective of the present study was to assess prognostic factors predictive for cerebral AVMs obliteration in 127 patients who underwent GKS. Methods: The AVMs were classified according to the Spetzler-Martin classification. Twenty-one cases (16.5 %) were classified as grade I, 46 cases (36.2 %) as grade II, 51 cases (40.1 %) as grade III, and nine cases (7.1 %) as grade IV-V. The AVMs were deeply located in 16.5 % of patients. The peripheral prescription dose ranged from 16 to 30 Gy (mean 22.3 Gy). The AVMs volume ranged from 0.1 to 13 cc (mean 2.7 cc). Results: In 72 patients out of the 104 (69.2 %) with a radiological follow-up, MRI showed the AVM obliteration; in 54 cases (60 %) out of the 90 that performed a DSA, a complete AVM obliteration was achieved (average closure time 48.5 months). The volume of the nidus (p = 0.001), the prescription dose (p = 0.004), the 2002 Pollock-Flickinger classification (p = 0.031), and their 2008 revised classification (p = 0.025) were found to be statistically significant in predicting the probability of AVM closure. In the multivariate analysis, only the prescription dose was found to be an independent prognostic factor (p = 0.009) for AVM obliteration. Conclusions: The volume of the nidus and the prescription dose significantly influence the outcome of radiosurgical treatment. The Pollock-Flickinger classification was found to be a reliable scoring system in predicting the AVM closure and an important tool for selection of patients candidate for GKS. © 2013 Springer-Verlag Wien."

Background: The treatment of choice for Cushing’s disease is pituitary surgery. Second-line treatments include repeat pituitary surgery, radiation therapy, medical therapy, and bilateral adrenalectomy. The most used modalities to irradiate patients with Cushing’s disease include fractionated radiotherapy and single-dose Gamma Knife. We aim to review the efficacy and safety of radiotherapy in patients with persistent or recurring Cushing’s disease. Results: Remission of Cushing’s disease after radiotherapy ranges from 42 to 83%. There seems to be no clear difference according to the technique of radiation used. Most patients experience remission of disease within 3 years from treatment, with only few cases reaching normal cortisol secretion after a longer follow-up. Control of tumor growth varies from 93 to 100%. Severe side effects of radiotherapy, such as optic neuropathy and radionecrosis, are uncommon. New-onset hypopituitarism is the most frequent side effect of radiation, occurring in 30–50% of patients treated by fractionated radiotherapy while it has been reported in 11–22% of patients after Gamma Knife. Conclusion: Radiotherapy is an effective second-line treatment in patients with Cushing’s disease not cured by surgery. Consideration of the advantages and disadvantages of radiotherapy in comparison with other therapeutic options should always be carried out in the single patient before deciding the second-line therapeutic strategy for persisting or recurring Cushing’s disease.

Background: Contrast-enhanced magnetic resonance (MR) imaging with gadolinium-based contrast agents is widely used for the detection of cerebral metastases with standard contrast agents. Newer developments in MR contrast agents have led to a higher relaxivity and/or concentration for these agents. Purpose: To assess the effectiveness of a standard dose of 1.0 M gadobutrol compared with a standard dose of gadopentetate dimeglumine for the MR detection of brain metastases. Material and Methods: 27 patients with at least one cerebral metastasis were examined twice with contrast-enhanced MR imaging, using gadobutrol at 0.1 ml/kg and gadopentetate dimeglumine at 0.2 ml/kg (i.e., identical gadolinium dosage of 0.1 mmol/kg bodyweight). The interval between examinations was 18 hours, and the order of injection was fully randomized. Images were acquired using a three-dimensional (3D) fast gradient echo sequence, and evaluated in blinded fashion by two experienced neuroradiologists in consensus in terms of the total number of lesions detected at each examination in each patient and qualitatively in terms of the lesion conspicuity observed. Results: A total of 67 lesions were detected after gadobutrol compared with 65 lesions detected after gadopentetate dimeglumine. In two patients, a lesion was seen only after gadobutrol. Qualitative comparison of images revealed improved lesion conspicuity after gadobutrol in 10/27 cases compared with 0/27 cases after gadopentetate dimeglumine, and equivalent conspicuity in 17/27 cases ( P=0.002, gadobutrol vs. gadopentetate dimeglumine). Conclusion:At equal gadolinium dosage, gadobutrol appears to offer significant advantages over gadopentetate dimeglumine for the visualization of brain metastases, with particular benefit for improving the conspicuity of detected lesions.

Purpose: To assess the utility of the Radiation Therapy Oncology Group Recursive Partitioning Analysis (RPA) and Score Index for Radiosurgery (SIR) stratification systems in predicting survival in patients with brain metastasis treated with Gamma Knife radiosurgery (GKRS). Methods and Materials: A total of 185 patients were included in the study. Patients were stratified according to RPA and SIR classes. The RPA and SIR classes, age, Karnofsky Performance Status (KPS), and systemic disease were correlated with survival. Results: Five patients were lost to follow-up. Median survival in patients in RPA Class 1 (30 patients) was 17 months; in Class 2 (140 patients), 10 months; and in Class 3 (10 patients), 3 months. Median survival in patients in SIR Class 1 (30 patients) was 3 months; in Class 2 (135 patients), 8 months; and in Class 3 (15 patients), 20 months. In univariate testing, age younger than 65 years (p = 0.0004), KPS higher than 70 (p = 0.0001), RPA class (p = 0.0078), SIR class (p = 0.0002), and control of the primary tumor (p = 0.02) were significantly associated with improved outcome. In multivariate analysis, KPS (p < 0.0001), SIR class (p = 0.0008), and RPA class (p = 0.03) had statistical value. Conclusions: This study supports the use of GKRS as a single-treatment modality in this selected group of patients. Stratification systems are useful in the estimation of patient eligibility for GKRS. A second-line treatment was necessary in 30% of patients to achieve distal or local brain control. This strategy is useful to control brain metastasis in long-surviving patients. (C) 2009 Elsevier Inc.

PURPOSE:: Positron emission tomography/computed tomography (PET/CT) with C-11 choline has been used for staging, restaging, and follow-up of various tumors, whereas its role for imaging meningiomas has only been preliminarily explored. The aim of this study was to compare C-11 choline and F-18 fluorodeoxyglucose (F-18 FDG) uptake in meningiomas and relate these findings to the histopathological analysis. METHODS:: Two sequential three-dimensional PET/CT scans with 370 MBq (10 mCi) of C-11 choline and 370 MBq (10 mCi) of F-18 FDG were performed 2 hours apart in 7 patients with histologically confirmed meningiomas. Five patients had WHO grade I and 2 had WHO grade II meningioma. For each scan, two-dimensional regions of interest were drawn on tumor boundaries and on the contralateral side on CT images and copied to the corresponding PET images. SUVmax and tumor-to-background ratio were calculated. RESULTS:: Relative to the contralateral side, C-11 choline uptake was increased in all meningiomas, whereas F-18 FDG uptake was decreased in 6 patients and increased in 1 of the 2 patients with grade II meningiomas. In the whole group, SUVmax of C-11 choline and F-18 FDG were 3.6 +/- 1.3 and 5.7 +/- 1.3, respectively. The tumor-to-background ratio for C-11 choline was much higher than that for F-18 FDG (5.3 +/- 0.8 vs. 0.9 +/- 0.2, respectively) (P < 0.001). The uptake of C-11 choline was higher in patients with grade II than in grade I meningiomas. CONCLUSIONS:: These preliminary results suggest that C-11 choline may better image meningiomas in comparison with F-18 FDG. Clinical applications of C-11 choline PET/CT for grading and follow-up of meningiomas need to be assessed in further studies.

Context: Single-session stereotactic radiotherapy (SR) may be a potential adjuvant treatment in acromegaly. Objective: We analyzed the safety and efficacy of SR in patients who had previously received maximal surgical debulking at our center. Design: The study was a retrospective analysis of hormonal, radiological, and ophthalmologic data collected in a predefined protocol from 1994 through 2006. Setting: The study was performed at a university hospital. Patients: Eighty-three acromegalic patients, 52 women and 31 men, with a mean age of 42.6 ± 1.2 yr, participated in the study. The median follow-up was 69 months (interquartile range 44–107 months). Intervention: The patients were treated with SR for residual or recurrent GH-secreting adenoma. Main Outcome Measure: Normalization of age- and sex-adjusted IGF-I levels together with a basal GH level below 2.5 μg/liter without concomitant GH-suppressive drugs was the goal of therapy. Results: Fifty patients (60.2%) reached the main outcome of the study. The rate of remission was 52.6% at 5 yr [95% confidence interval (CI) 40.6–64.6%]. Another 13 patients (15.7%), who were resistant to somatostatin analogs, were in remission after SR. Multivariate analysis showed that low basal GH and IGF-I levels were associated with a favorable outcome. No serious side effects occurred after SR. The 5-yr cumulative risk of new onset hypogonadism, hypothyroidism, or hypoadrenalism was 3.6% (95% CI 0–8.6%), 3.3% (95% CI 0–7.7%), and 4.9% (95% CI 0–10.4%), respectively. Conclusion: In a highly selected group of acromegalic patients, SR treatment had good efficacy and safety. This may lead to reconsider the role of SR in the therapeutic algorithm of acromegaly.

Contrast-enhanced magnetic resonance (MR) imaging is considered the most sensitive method for detecting tumors in the central nervous system (CNS). The primary objective is to improve lesion detection, delineation, and characterization (benign or malignant) in order to more accurately define the location, extent, and type of disease and the appropriate treatment option for improved patient outcome (surgical intervention, radiation therapy or cytotoxic chemotherapy). This article reviews the various types of tumor occurring in the brain and the specific role of contrast-enhanced MR imaging for the evaluation of these tumors. Emphasis is placed on the value of contrast-enhanced MR imaging in the evaluation of primary intra-axial brain lesions and how high relaxivity contrast agents such as MultiHance (Bracco Imaging, Milan, Italy) might improve detection, treatment planning, and follow-up.

Object The goal in this article was to compare 0.1 mmol/kg doses of gadobenate dimeglumine (Gd-BOPTA) and gadopentetate dimeglumine, also known as gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), for enhanced magnetic resonance (MR) imaging of intraaxial brain tumors. Methods Eighty-four patients with either intraaxial glioma (47 patients) or metastasis (37 patients) underwent two MR imaging examinations at 1.5 tesla, one with Gd-BOPTA as the contrast agent and the other with Gd-DTPA. The interval between fully randomized contrast medium administrations was 2 to 7 days. The T1-weighted spin echo and T2-weighted fast spin echo images were acquired before administration of contrast agents and T1-weighted spin echo images were obtained after the agents were administered. Acquisition parameters and postinjection acquisition times were identical for the two examinations in each patient. Three experienced readers working in a fully blinded fashion independently evaluated all images for degree and quality of available information (lesion contrast enhancement, lesion border delineation, definition of disease extent, visualization of the lesion's internal structures, global diagnostic preference) and quantitative enhancement (that is, the extent of lesion enhancement after contrast agent administration compared with that seen before its administration [hereafter referred to as percent enhancement], lesion/brain ratio, and contrast/noise ratio). Differences were tested with the Wilcoxon signed-rank test. Reader agreement was assessed using kappa statistics. Significantly better diagnostic information/imaging performance (p < 0.0001, all readers) was obtained with Gd-BOPTA for all visualization end points. Global preference for images obtained with Gd-BOPTA was expressed for 42 (50%), 52 (61.9%), and 56 (66.7%) of 84 patients (readers 1, 2, and 3, respectively) compared with images obtained with Gd-DTPA contrast in four (4.8%), six (7.1%), and three (3.6%) of 84 patients. Similar differences were noted for all other visualization end points. Significantly greater quantitative contrast enhancement (p < 0.04) was noted after administration of Gd-BOPTA. Reader agreement was good (κ > 0.4). Conclusions Lesion visualization, delineation, definition, and contrast enhancement are significantly better after administration of 0.1 mmol/kg Gd-BOPTA, potentially allowing better surgical planning and follow up and improved disease management.

The most frequently used target for DBS in advanced Parkinson Disease (PD) is the sensorimotor subthalamic nucleus (STN), anatomically referred to as dorso-lateral STN [3]. Ambiguities arise, regarding the true meaning of this description in the STN. Does "dorsal" indicate posterior or superior? At its best, this definition assigns two directions in space to a three-dimensional structure.This paper evaluates the ambiguity and describes the sensorimotor part of the STN in stereotactic space.

Intracranial metastases are the most common form of intra-axial brain tumor. Management approaches to brain metastases include surgical resection, whole-brain radiotherapy, and stereotactic radiosurgery (SRS). The management approach that is selected is based typically on algorithms that incorporate the number, size, and location of lesions. SRS is the treatment of choice when metastases detected on imaging are few (maximum, 3-5) and/or of small size (≤30 mm) and offers the advantages of noninvasiveness and the ability to treat inaccessible lesions compared with surgical resection. Contrast-enhanced magnetic resonance imaging (MRI) is the standard imaging technique for determining the number, size, and location of metastatic lesions. In SRS, the capability of MRI to delineate lesion borders precisely in 3 dimensions helps reduce recurrence rates and minimize radiation necrosis in surrounding tissue. Optimization of the MRI protocol, including selection of the appropriate gadolinium-based contrast agent (GBCA), is paramount for accurate lesion imaging. GBCAs differ in their safety, tolerability, and efficacy because of their diverse physicochemical properties. Gadobutrol and gadobenate dimeglumine are high-relaxivity GBCAs that demonstrate superior efficacy for imaging metastatic lesions compared with other GBCAs, whereas gadobutrol additionally provides macrocyclic stability. This article reviews recent comparative trials of GBCAs and discusses their relevance for optimizing MRI protocols in the management of brain metastases, with particular relevance to SRS. ABBREVIATIONS:: CNR, contrast-to-noise ratioCNS, central nervous systemGBCA, gadolinium-based contrast agentNSF, nephrogenic systemic fibrosisSRS, stereotactic radiosurgeryWBRT, whole-brain radiotherapy. © 2013 by the Congress of Neurological Surgeons.

Introduction Uveal melanoma (UM) is a life threatening intraocular malignant tumor. Gamma Knife Stereotactic Radiosurgery (GKSRS) is a well-assessed strategy for conservative treatment of UM providing good results for survival, local control and eye preservation. Purpose Our aim is to develop predictive models for radio-induced effects in UM patients treated with exclusive GKSRS. Materials and methods Medical records and 3D dosimetry data of critical structures of 66 patients were retrospectively reviewed. Cox’s proportional hazard model was used to identify clinical and dosimetric variables as independent risk factor for most clinically relevant GKSRS-related complications: radiation vasculopathy(RV), radiation papillopathy (RP) and neovascular glaucoma(NVG), visual acuity(VA) reduction >20% (VA20%) and complete loss of basal VA (VA100%). ROC curve analysis allowed predicting cutoff values of significant variables. Results The 2 years incidences were: RV 10%, RP 12%, NVG 14%, VA20% 59% and VA100% 27%. A clear relationship with D1% to optic nerve (ON) was found for RP and RV. Also, for RV, the prescription isodose-ON distance (PIOND) and the anterior to equator position of the tumor resulted as protective variables. The V20 of posterior segment and tumor thickness were predictive for NVG. Multivariate analyses resulted in two variables predictive model both for VA20% and VA100%, including tumor largest diameter and D1% to ON. A second predictive model, including PIOND, was found for VA100%. Conclusion We found clinical and dosimetric variables to predict the risk of main side effects after GKSRS for UM. These results may provide new dose constraints to critical structures potentially able to reduce toxicities. Disclosure Antonella del Vecchio has a contract as starter-up with Elekta Instrument AB. No other conflict of interest to declare for the other authors.

MR imaging is the preferred technique for the diagnosis, treatment planning, and monitoring of patients with neoplastic CNS lesions. Conventional MR imaging, with gadolinium-based contrast enhancement, is increasingly combined with advanced, functional MR imaging techniques to offer morphologic, metabolic, and physiologic information. This article provides updated recommendations to neuroradiologists, neuro-oncologists, neurosurgeons, and radiation oncologists on the practical applications of MR imaging of neoplastic CNS lesions in adults, with particular focus on gliomas, based on a review of the clinical trial evidence and personal experiences shared at a recent international meeting of experts in neuroradiology, neuro-oncology, neurosurgery, and radio-oncology.

Objective. Single-session radiosurgery with Gamma Knife (GK) may be a potential adjuvant treatment in acromegaly. We analyzed the safety and efficacy of GK in patients who had previously received maximal surgical debulking at our hospital.Methods. The study was a retrospective analysis of hormonal, radiological, and ophthalmologic data collected in a predefined protocol from 1994 to 2009. The mean age at treatment was 42.3 years (range 22–67 yy). 103 acromegalic patients participated in the study. The median follow-up was 71 months (IQ range 43–107). All patients were treated with GK for residual or recurrent GH-secreting adenoma.Results. Sixty-three patients (61.2%) reached the main outcome of the study. The rate of remission was 58.3% at 5 years (95% CI 47.6–69.0%). Other 15 patients (14.6%) were in remission after GK while on treatment with somatostatin analogues. No serious side effects occurred after GK. Eight patients (7.8%) experienced a new deficit of pituitary function. New cases of hypogonadism, hypothyroidism, and hypoadrenalism occurred in 4 of 77 patients (5.2%), 3 of 95 patients (3.2%), and 6 of 100 patients at risk (6.0%), respectively.Conclusion. In a highly selected group of acromegalic patients, GK treatment had good efficacy and safety.

To evaluate clinical and physico-dosimetric variables affecting clinical outcome of patients treated with Gamma Knife radiosurgery (GKRS) for brain metastases from non-small cell lung cancer (NSCLC).Between 2001 and 2006, 373 patients (298 men and 75 women, median age 65 years) with brain metastases from NSCLC underwent GKRS. All of them had KPS ≥ 60%, eight or fewer brain metastases, confirmed histopathological diagnosis and recent work-up (3 months). Thirty-five patients belonged to recursive partitioning analysis (RPA) Class I, 307 patients were in RPA Class II, 7 patients were in RPA Class III. Median tumor volume was 3.6 cm(3). Median marginal dose was 22.5 Gy at 50% isodose.; median 10 Gy and 12 Gy isodose volumes were 30.8 cm(3) and 15.8 cm(3), respectively. Follow-up with MRI was performed every 3 months. Overall survival data were collected from internal database, telephone interviews, and identifying registries.Mean follow-up after GKRS was 51 months (range, 6 to 96 months); mean overall survival was 14.2 months. Of 373 patients, 29 were alive at time of writing, 104 had died of cerebral progression, and 176 had died of systemic progression. In 64 cases it was not possible to ascertain the cause. Univariate and multivariate analysis were adjusted for the following: RPA class, surgery, WBRT, age, gender, number of lesions, median tumor volume, median peripheral dose, and 10 Gy and 12 Gy volumes. Identified RPA class and overall tumor volume5 cc were the only two covariates independently predictive of overall survival in patients who died of cerebral progression.Global volume of brain disease should be the main parameter to consider for performing GKRS, which is a first-line therapy for patient in good general condition and controlled systemic disease.

Object Due to technological advances in neuroradiology in recent years, incidental diagnoses of vestibular schwannomas (VSs) have increased. The aim of this study was to evaluate the hearing function after treatment with Gamma Knife surgery (GKS) for VSs in patients adequately selected with “good” or “useful” hearing before treatment and to assess the possible predictive factors for hearing function preservation. Methods Of all patients treated in the authors' hospital between 2001 and 2007, they retrospectively studied 50 patients with a unilateral VS in whom there was serviceable hearing (Gardner-Robertson [GR] Class I or II). Additional inclusion criteria were: no Type 2 neurofibromatosis, no previous treatment, and at least 6 months' follow-up of neuroradiological and audiological data. The median patient age was 54 years (range 24–78 years). The median tumor volume was 0.73 ml (range 0.03–6.6 ml), and the median radiation dose to the tumor margin was 13 Gy (range 12–16 Gy) with an isodose of 50%. Results Patient age, tumor volume, and presenting symptoms were found to correlate with hearing function. At a median of 36 months after radiosurgery, tumor growth control was 96% and no patient required any other additional treatment. Serviceable hearing was preserved in 34 patients (68%): 21 (62%) with GR Class I hearing and 13 (38%) with GR Class II hearing. The remaining 16 patients had poor hearing function:15 with GR Class III and 1 with GR Class IV hearing function. In 19 (58%) of 33 patients with GR Class I function before GKS the same class was maintained posttreatment; 29 (88%) maintained functional hearing (GR Class I or II). In all patients with an intracanalicular lesion, functional hearing was maintained. Significant prognostic factors for maintaining serviceable hearing were GR Class I function before treatment, symptoms at presentation, patient age younger than 54 years, and Koos Stage T1 disease. Conclusions The results of the study show that the probability of preserving functional hearing in patients undergoing GKS treatment for unilateral VSs is very high. Patients with GR Class I, age younger than 54 years, with presenting symptoms other than hearing loss, and a Koos Stage T1 tumor have better prognosis. The prescribed dose of 13 Gy appears to represent an excellent compromise between controlling the disease and preserving auditory function.

To present our treatment protocol and evaluate the results of Gamma knife radiosurgery (GKR) in treating patients with uveal melanoma.Seventy-eight consecutive patients with uveal melanoma underwent stereotactic radiosurgery (radiation dose 30-50 Gy) with a Leksell Gamma-Knife at the San Raffaele University Hospital, Milan, Italy between 1994 and 2006. The main outcome measures evaluated were: survival rate, local tumour control, eye retention rate, visual acuity and treatment-related complications.Survival rate was 88.8% at 3 years and 81.9% at 5 years. Local tumour control was achieved in 91.0% of patients. The median tumour thickness reduction after treatment was 1.96 mm (p0.0001) (-32.1%). The eye retention rate was 89.7%. A significant relative reduction of visual acuity was observed during follow-up. The most frequent treatment-related complications were: exudative retinopathy (33.3%), neovascular glaucoma (18.7%), radiogenic retinopathy (13.5%) and vitreous haemorrhages (10.4%).GKR can be considered an alternative to enucleation for the treatment of choroidal melanomas.

Object Treatment options for patients with cavernous sinus meningiomas (CSMs) include microsurgical tumor resection, radiotherapy, and radiosurgery. Gamma Knife surgery (GKS) is increasingly being used because it is associated with lower mortality and morbidity rates than microsurgery. The purpose of this study was to assess the role of GKS in the treatment of CSM and to thoroughly analyze the clinical response to GKS. Methods Between January 2001 and December 2005, 123 patients (25 men and 98 women; mean age 62.6 ± 11 years, range 31–86 years) who underwent treatment for CSMs were included in this study. Of these, 41 patients underwent microsurgery before GKS, whereas the remaining 82 had GKS as a first-line therapy after a diagnosis was made based on magnetic resonance imaging findings. Dysfunction in cranial nerves (CNs) II, III, IV, V, and VI was noted in 74 patients at the time of GKS. The mean tumor volume was 7.99 cm3 (0.7–30.5 cm3). The mean prescription dose to the tumor margin was 13.8 ± 1.1 Gy (range 10–20 Gy). Results The overall tumor control rate was 98.4% with a median follow-up of 36 months. The actuarial tumor control rate at 5 years was 90.5%. A reduction in tumor volume was observed in 53 patients (43.1%), whereas in 68 patients (55.3%) no volumetric variation was recorded. Of the 74 patients who presented with CN deficits, improvement was noted in 23 (31.1%). Conclusions Gamma Knife surgery is a useful treatment for CSM both as a first- or second-line therapy. It is a safe and effective treatment for tumors located close to the optic pathways.

The authors assessed MATILDE chemotherapy followed by response-tailored radiation therapy in 41 patients aged 70 years or younger with primary CNS lymphoma in a Phase II trial. With response rates of 76% after MATILDE and 83% after chemotherapy with or without radiation therapy, this was an active strategy, particularly in low- to intermediate-risk patients (International Extranodal Lymphoma Study Group [IELSG] score). Myelosuppression was the dose-limiting toxicity, with 9.5% of lethal complications. After a median follow-up of 49 months, a plateau in the survival curve (5-year overall survival: 41 +/- 7%) was obtained.

Object. The authors studied the efficacy of gamma knife radiosurgery (GKS) in the prevention of regrowth of nonfunctioning pituitary adenomas (NPA). Methods. One hundred nineteen patients were included in this study and were divided into two groups. All patients had undergone surgery in our department and recurrent or residual adenoma was demonstrated on postoperative MR imaging. Group A consisted of 68 patients who were followed without additional treatment. Group B was composed of 51 patients who received GKS within 1 year after microsurgery. There was no significant demographic difference between the two groups. In Group B the mean margin dose was 16.5 ± 0.3 Gy (range 13–21 Gy). Fifty one and one tenth percent of patients in Group A were recurrence free at 5 years and 89.8% in Group B (p < 0.001). In Group B patients, tumor volume decreased from a baseline value of 2.4 ± 0.2 cm3 to 1.6 ± 0.2 cm3 at last follow up (p < 0.001). Conclusions. The results of this study suggest that GKS is effective in controlling growth of residual NPA for at least 5 years following initial maximal surgical debulking compared with no radiation therapy. Thus, GKS is recommended after microsurgery when visible tumor can be detected on imaging studies.

A quantitative technique utilising [14C]α-aminoisobutyric acid as a tracer was used to study cerebrovascular permeability in 22 Mongolian gerbils. Seven other animals were used to measure cerebral blood volumes. Global cerebral ischaemia was produced by temporary bilateral carotid artery occlusion (60 min) in 16 gerbils that were sacrificed at 1, 2, and 3 h following reperfusion. The blood-to-brain transfer constant was significantly increased after 2 h of reperfusion in the ischaemic zones and also in structures, like the cerebellum, not supplied by the carotid artery and not ischaemic during the vessel occlusion. The blood-brain barrier (BBB) alterations were coincident with the onset of ischaemia—induced seizures that were accompanied by sudden “spikes” of systemic blood pressure. Epilepsy may play an important role in the development of BBB damage in this ischaemic model, and this factor must be considered in the interpretation of BBB damage data in gerbils.

Fifteen patients with definite multiple sclerosis were examined with high volume delayed (HVD) CT scan and positron emission tomography (PET) using 68-Ga-EDTA as a tracer. The passage of 68-Ga-EDTA across the blood-brain barrier (BBB) was measured by using multiple graphical analysis. This method permits the simultaneous calculation of a blood to brain influx constant Ki (ml/g-1 min-1) and of the plasma volume Vp (ml/g-1). Focal areas of abnormal CT enhancement and pathological accumulation of 68-Ga-EDTA were visualised in four patients who were all examined during a clinical exacerbation of the disease. The mean Ki value measured in these areas was 12.5, SD 3.4 indicating a moderate but significant increase of BBB permeability compared with the value found in normal tissue (3.2, SD 0.9). No parallel increase in Vp values was found in these pathological areas. Quantitative data obtained with PET seems to provide further insight into the study of BBB function in multiple sclerosis.