In-silico trial of intracranial flow diverters replicates and expands insights from conventional clinical trials.

The cost of clinical trials is ever-increasing. In-silico trials rely on virtual populations and interventions simulated using patient-specific models and may offer a solution to lower these costs. We present the flow diverter performance assessment (FD-PASS) in-silico trial, which models the treatment of intracranial aneurysms in 164 virtual patients with 82 distinct anatomies with a flow-diverting stent, using computational fluid dynamics to quantify post-treatment flow reduction. The predicted FD-PASS flow-diversion success rates replicate the values previously reported in three clinical trials. The in-silico approach allows broader investigation of factors associated with insufficient flow reduction than feasible in a conventional trial. Our findings demonstrate that in-silico trials of endovascular medical devices can: (i) replicate findings of conventional clinical trials, and (ii) perform virtual experiments and sub-group analyses that are difficult or impossible in conventional trials to discover new insights on treatment failure, e.g. in the presence of side-branches or hypertension.

Aneurysm Treatment With Woven EndoBridge in the Cumulative Population of 3 Prospective, Multicenter Series: 2-Year Follow-Up.

BACKGROUND: Woven EndoBridge (WEB; Sequent Medical) treatment is an innovative endovascular approach for treatment of wide-neck bifurcation aneurysms. Initial studies have shown high safety with good efficacy at short term confirmed by trials conducted in United States (WEB-Intrasaccular Therapy) and in Europe (WEB Clinical Assessment of Intrasaccular Aneurysm Therapy [WEBCAST], French Observatory, and WEBCAST-2). OBJECTIVE: To report the 2-yr clinical and anatomical results of WEB treatment in the combined population of 3 European trials. METHODS: In a French Observatory, 2-yr clinical and anatomical data were collected. In WEBCAST and WEBCAST-2, 2-yr follow-up was optional, and data were collected when follow-up was performed. Aneurysm occlusion was evaluated using a 3-grade scale: complete occlusion, neck remnant, and aneurysm remnant. RESULTS: The population for safety was 138/168 patients (82.1%), including 89 females (64.5%), with mean age of 55.5 ± 10.2 yr. The population for efficacy was 121/169 aneurysms (71.6%). Aneurysm locations were middle cerebral artery in 65/121 aneurysms (53.7%), anterior-communicating artery in 25/121 (20.7%), basilar artery in 17/121 (14.0%), and internal carotid artery terminus in 14/121 (11.6%). No clinically relevant adverse events occurred between years 1 and 2. At 2 yr, complete occlusion was observed in 62/121 (51.2%) aneurysms, neck remnant in 36/121 (29.8%) aneurysms, and aneurysm remnant in 23/121 (19.0%) aneurysms. The global retreatment rate at 2 yr was 9.3%. CONCLUSION: This analysis confirms the high safety profile of WEB treatment at 2 yr. Aneurysm occlusion is generally stable at 2 yr, and the retreatment rate between 1 yr and 2 yr is low (2.0%).

The safety and effectiveness of the Woven EndoBridge (WEB) system for the treatment of wide-necked bifurcation aneurysms: final 12-month results of the pivotal WEB Intrasaccular Therapy (WEB-IT) Study.

INTRODUCTION: The Woven EndoBridge Intrasaccular Therapy (WEB-IT) Study is a pivotal, prospective, single-arm, investigational device exemption study designed to evaluate the safety and effectiveness of the WEB device for the treatment of wide-neck bifurcation aneurysms. METHODS: One-hundred and fifty patients with wide-neck bifurcation aneurysms were enrolled at 21 US and six international centers. Angiograms from the index procedure, and 6-month and 1-year follow-up visits were all reviewed by a core laboratory. All adverse events were reviewed and adjudicated by a clinical events adjudicator. A data monitoring committee provided oversight during the trial to ensure subject safety. RESULTS: One-hundred and forty-eight patients received the WEB implant. One (0.7%) primary safety event occurred during the study-a delayed ipsilateral parenchymal hemorrhage-on postoperative day 22. No primary safety events occurred after 30 days through 1 year. At the 12-month angiographic follow-up, 77/143 patients (53.8%) had complete aneurysm occlusion. Adequate occlusion was achieved in 121/143 (84.6%) subjects. CONCLUSIONS: The prespecified safety and effectiveness endpoints for the aneurysms studied in the WEB-IT trial were met. The results of this trial suggest that the WEB device provides an option for patients with wide-neck bifurcation aneurysms that is as effective as currently available therapies and markedly safer. TRIAL REGISTRATION NUMBER: NCT02191618.

Visualizing artery-specific blood flow patterns above the circle of Willis with vessel-encoded arterial spin labeling.

PURPOSE: To establish the feasibility of using vessel-encoded pseudocontinuous arterial spin labeling (VEPCASL) for noninvasive vascular territory imaging (VTI) and artery-specific dynamic angiography of a large number of arterial branches above the circle of Willis within a clinically feasible scan time. METHODS: 3D time-of-flight angiography was used to select a labeling plane and establish 7 pairs of encoding cycles. These were used for VEPCASL VTI and dynamic 2D angiography (8 min and 3 min acquisition times, respectively) in healthy volunteers, allowing the separation of signals arising from 13 arterial branches (including extracranial arteries) in postprocessing. To demonstrate the clinical potential of this approach, VEPCASL angiography was also applied in 5 patients with brain arteriovenous malformation (AVM). RESULTS: In healthy volunteers, the artery-specific filling of the vascular tree and resulting perfusion territories were well depicted. SNRs were approximately 5 times higher than those achievable with single-artery selective methods. Blood supply to the AVMs was well visualized in all cases, showing the main feeding arteries and venous drainage. CONCLUSIONS: VEPCASL is a highly efficient method for both VTI and dynamic angiography of a large number of arterial branches, providing a comprehensive picture of vascular flow patterns and the effect on downstream tissue perfusion within an acceptable scan time. Automation of labeling plane and vessel-encoding selection would improve robustness and efficiency, and further refinement could allow quantitative blood flow measurements to be obtained. This technique shows promise for visualizing the blood supply to lesions and collateral flow patterns.

Thrombosis in Cerebral Aneurysms and the Computational Modeling Thereof: A Review.

Thrombosis is a condition closely related to cerebral aneurysms and controlled thrombosis is the main purpose of endovascular embolization treatment. The mechanisms governing thrombus initiation and evolution in cerebral aneurysms have not been fully elucidated and this presents challenges for interventional planning. Significant effort has been directed towards developing computational methods aimed at streamlining the interventional planning process for unruptured cerebral aneurysm treatment. Included in these methods are computational models of thrombus development following endovascular device placement. The main challenge with developing computational models for thrombosis in disease cases is that there exists a wide body of literature that addresses various aspects of the clotting process, but it may not be obvious what information is of direct consequence for what modeling purpose (e.g., for understanding the effect of endovascular therapies). The aim of this review is to present the information so it will be of benefit to the community attempting to model cerebral aneurysm thrombosis for interventional planning purposes, in a simplified yet appropriate manner. The paper begins by explaining current understanding of physiological coagulation and highlights the documented distinctions between the physiological process and cerebral aneurysm thrombosis. Clinical observations of thrombosis following endovascular device placement are then presented. This is followed by a section detailing the demands placed on computational models developed for interventional planning. Finally, existing computational models of thrombosis are presented. This last section begins with description and discussion of physiological computational clotting models, as they are of immense value in understanding how to construct a general computational model of clotting. This is then followed by a review of computational models of clotting in cerebral aneurysms, specifically. Even though some progress has been made towards computational predictions of thrombosis following device placement in cerebral aneurysms, many gaps still remain. Answering the key questions will require the combined efforts of the clinical, experimental and computational communities.

Outcome of Nonfunctioning Pituitary Adenomas That Regrow After Primary Treatment: A Study From Two Large UK Centers.

Context: Despite the major risk of regrowth of clinically nonfunctioning pituitary adenomas (CNFAs) after primary treatment, systematic data on the probability of further tumor progression and the effectiveness of management approaches are lacking. Objective: To assess the probability of further regrowth(s), predictive factors, and outcomes of management approaches in patients with CNFA diagnosed with adenoma regrowth after primary treatment. Patients, Design, and Setting: Retrospective cohort study of 237 patients with regrown CNFA managed in two UK centers. Results: Median follow-up was 5.9 years (range, 0.4 to 37.7 years). The 5-year second regrowth rate was 35.3% (36.2% after surgery; 12.5% after radiotherapy; 12.7% after surgery combined with radiotherapy; 63.4% with monitoring). Of those managed with monitoring, 34.8% eventually were offered intervention. Type of management and sex were risk factors for second regrowth. Among those with second adenoma regrowth, the 5-year third regrowth rate was 26.4% (24.4% after surgery; 0% after radiotherapy; 0% after surgery combined with radiotherapy; 48.3% with monitoring). Overall, patients with a CNFA regrowth had a 4.4% probability of a third regrowth at 5 years and a 10.0% probability at 10 years; type of management of the first regrowth was the only risk factor. Malignant transformation was diagnosed in two patients. Conclusions: Patients with regrown CNFA after primary treatment continue to carry considerable risk of tumor progression, necessitating long-term follow-up. Management approach to the regrowth was the major factor determining this risk; monitoring had >60% risk of progression at 5 years, and a substantial number of patients ultimately required intervention.

Time density curve analysis for C-arm FDCT PBV imaging.

INTRODUCTION: Parenchymal blood volume (PBV) estimation using C-arm flat detector computed tomography (FDCT) assumes a steady-state contrast concentration in cerebral vasculature for the scan duration. Using time density curve (TDC) analysis, we explored if the steady-state assumption is met for C-arm CT PBV scans, and how consistent the contrast-material dynamics in cerebral vasculature are across patients. METHODS: Thirty C-arm FDCT datasets of 26 patients with aneurysmal-SAH, acquired as part of a prospective study comparing C-arm CT PBV with MR-PWI, were analysed. TDCs were extracted from the 2D rotational projections. Goodness-of-fit of TDCs to a steady-state horizontal-line-model and the statistical similarity among the individual TDCs were tested. Influence of the differences in TDC characteristics on the agreement of resulting PBV measurements with MR-CBV was calculated. RESULTS: Despite identical scan parameters and contrast-injection-protocol, the individual TDCs were statistically non-identical (p < 0.01). Using Dunn's multiple comparisons test, of the total 435 individual comparisons among the 30 TDCs, 330 comparisons (62%) reached statistical significance for difference. All TDCs deviated significantly (p < 0.01) from the steady-state horizontal-line-model. PBV values of those datasets for which the TDCs showed largest deviations from the steady-state model demonstrated poor agreement and correlation with MR-CBV, compared with the PBV values of those datasets for which the TDCs were closer to steady-state. CONCLUSION: For clinical C-arm CT PBV examinations, the administered contrast material does not reach the assumed 'ideal steady-state' for the duration of scan. Using a prolonged injection protocol, the degree to which the TDCs approximate the ideal steady-state influences the agreement of resulting PBV measurements with MR-CBV.

Whole brain C-arm computed tomography parenchymal blood volume measurements.

INTRODUCTION: C-arm flat detector computed tomography (FDCT) parenchymal blood volume (PBV) imaging in the neuro-interventional suite is a new technique for which detailed whole brain measurements have not been previously reported. This study aims to create a catalogue of PBV measurements for various anatomical regions encompassing the whole brain, using a three-dimensional volume-of-interest (3D-VOI) analysis. METHODS: We acquired and analysed 30 C-arm FDCT datasets from 26 patients with aneurysmal subarachnoid haemorrhage (SAH), as part of a prospective study comparing C-arm computed tomography (CT) PBV with magnetic resonance perfusion-weighted imaging (MR-PWI). We calculated the PBV values for various brain regions with an automated analysis, using 58 pre-defined atlas-based 3D-VOIs encompassing the whole brain. VOIs partially or completely overlapping regions of magnetic resonance diffusion weighted imaging (MR-DWI) abnormality or magnetic resonance cerebral blood flow (MR-CBF) asymmetry were excluded from the analysis. RESULTS: Of the 30 C-arm CT PBV datasets, 14 (54%; 12 patients) had areas of restricted diffusion, the majority of which were focal. The PBV values for the cerebral cortex and cerebral white matter were 4.01 ± 0.47 (mean ± SD) and 3.01 ± 0.39 ml per 100 ml. Lobar PBV values were: frontal lobe 4.2 ± 0.8, temporal lobe 4.2 ± 0.9, parietal lobe 3.9 ± 0.7 and occipital lobe 4.3 ± 0.8 ml/100 ml. The basal ganglia and brainstem PBV values were 3.4 ± 0.7 and 4.6 ± 0.6 ml/100 ml, respectively. CONCLUSIONS: Compared with the typical reference cerebral blood volume (CBV) values reported in the literature for Positron Emission Tomography (PET), the PBV values were relatively high for the white matter and relatively low for the cortical grey matter. The reported catalogue of PBV values for various brain regions would be useful to inform future studies and could be used in clinical practice, when interpreting PBV maps.

Safety and efficacy of aneurysm treatment with WEB: results of the WEBCAST study.

OBJECT WEB is an innovative intrasaccular treatment for intracranial aneurysms. Preliminary series have shown good safety and efficacy. The WEB Clinical Assessment of Intrasaccular Aneurysm Therapy (WEBCAST) trial is a prospective European trial evaluating the safety and efficacy of WEB in wide-neck bifurcation aneurysms. METHODS Patients with wide-neck bifurcation aneurysms for which WEB treatment was indicated were included in this multicentergood clinical practices study. Clinical data including adverse events and clinical status at 1 and 6 months were collected and independently analyzed by a medical monitor. Six-month follow-up digital subtraction angiography was also performed and independently analyzed by a core laboratory. Success was defined at 6 months as complete occlusion or stable neck remnant, no worsening in angiographic appearance from postprocedure, and no retreatment performed or planned. RESULTS Ten European neurointerventional centers enrolled 51 patients with 51 aneurysms. Treatment with WEB was achieved in 48 of 51 aneurysms (94.1%). Adjunctive implants (coils/stents) were used in 4 of 48 aneurysms (8.3%). Thromboembolic events were observed in 9 of 51 patients (17.6%), resulting in a permanent deficit (modified Rankin Scale [mRS] Score 1) in 1 patient (2.0%). Intraoperative rupture was not observed. Morbidity (mRS score > 2) and mortality were 2.0% (1 of 51 patients, related to rupture status on entry to study) and 0.0% at 1 month, respectively. Success was achieved at 6 months in 85.4% of patients treated with WEB: 23 of 41 patients (56.1%) had complete occlusion, 12 of 41 (29.3%) had a neck remnant, and 6 of 41 (14.6%) had an aneurysm remnant. CONCLUSIONS The WEBCAST study showed good procedural and short-term safety of aneurysm treatment with WEB and good 6-month anatomical results.

Mortality in patients with non-functioning pituitary adenoma is increased: systematic analysis of 546 cases with long follow-up.

OBJECTIVE: Non-functioning pituitary adenomas (NFAs) have a prevalence of 7-22/100,000 people. A significant number of patients suffer from morbidities related to the tumor, possible recurrence(s), and treatments utilized. Our aim was to assess mortality of patients with macroNFA and predictive factors. DESIGN: Retrospective cohort study in a tertiary referral center in the UK. METHODS: A total of 546 patients operated for a macroNFA between 1963 and 2011 were studied. Mortality data were retrieved through the National Health Service Central Register and hospital records and recorded as standardized mortality ratio (SMR). Mortality was estimated for the total and various subgroups with clinical follow-up data. RESULTS: Median follow-up was 8 years (range: 1 month-48.5 years). SMR was 3.6 (95% CI, 2.9-4.5), for those operated before 1990, 4.7 (95% CI, 2.7-7.6) and for those after 1990, 3.5 (95% CI, 2.8-4.4). Main causes of death were cardio/cerebrovascular (33.7%), infections (30.1%), and malignancy (28.9%). Cox regression analysis demonstrated that only age at diagnosis remained an independent predictor of mortality (hazard ratio 1.10; 95% CI, 1.07-1.13, P<0.001), whereas sex, presentation with acute apoplexy, extent of tumor removal, radiotherapy, recurrence, untreated GH deficiency, FSH/LH deficiency, ACTH deficiency, TSH deficiency, and treatment with desmopressin had no impact. CONCLUSIONS: Despite the improvement of treatments over the last three decades, the mortality of patients with NFAs in our series remains high. Apart from age, factors related with the management/outcome of the tumor are not independent predictors, and pituitary hormone deficits managed with the currently-used substitution protocols do not adversely affect mortality.

Non-invasive assessment of vasospasm following aneurysmal SAH using C-arm FDCT parenchymal blood volume measurement in the neuro-interventional suite: Technical feasibility.

INTRODUCTION: Cerebral vasospasm is the leading cause of morbidity and mortality in patients with aneurysmal subarachnoid haemorrhage (SAH) surviving the initial ictus. Commonly used techniques for vasospasm assessment are digital subtraction angiography and transcranial Doppler sonography. These techniques can reliably identify only the major vessel spasm and fail to estimate its haemodynamic significance. To overcome these issues and to enable comprehensive non-invasive assessment of vasospasm inside the interventional suite, a novel protocol involving measurement of parenchymal blood volume (PBV) using C-arm flat detector computed tomography (FDCT) was implemented. MATERIALS AND METHODS: Patients from the neuro-intensive treatment unit (ITU) with suspected vasospasm following aneurysmal SAH were scanned with a biplane C-arm angiography system using an intravenous contrast injection protocol. The PBV maps were generated using prototype software. Contemporaneous clinically indicated MR scan including the diffusion- and perfusion-weighted sequences was performed. C-arm PBV maps were compared against the MR perfusion maps. RESULTS: Distribution of haemodynamic impairment on C-arm PBV maps closely matched the pattern of abnormality on MR perfusion maps. On visual comparison between the two techniques, the extent of abnormality indicated PBV to be both cerebral blood flow and cerebral blood volume weighted. CONCLUSION: C-arm FDCT PBV measurements allow an objective assessment of the severity and localisation of cerebral hypoperfusion resulting from vasospasm. The technique has proved feasible and useful in very sick patients after aneurysmal SAH. The promise shown in this early study indicates that it deserves further evaluation both for post-SAH vasospasm and in other relevant clinical settings.

C-arm flat detector computed tomography parenchymal blood volume imaging: the nature of parenchymal blood volume parameter and the feasibility of parenchymal blood volume imaging in aneurysmal subarachnoid haemorrhage patients.

INTRODUCTION: C-arm flat detector computed tomography (FDCT) parenchymal blood volume (PBV) measurements allow assessment of cerebral haemodynamics in the neurointerventional suite. This paper explores the feasibility of C-arm computed tomography (CT) PBV imaging and the relationship between the C-arm CT PBV and the MR-PWI-derived cerebral blood volume (CBV) and cerebral blood flow (CBF) parameters in aneurysmal subarachnoid haemorrhage (SAH) patients developing delayed cerebral ischemia (DCI). METHODS: Twenty-six patients with DCI following aneurysmal SAH underwent a research C-arm CT PBV scan using a biplane angiography system and contemporaneous MR-PWI scan as part of a prospective study. Quantitative whole-brain atlas-based volume-of-interest analysis in conjunction with Pearson correlation and Bland-Altman tests was performed to explore the agreement between C-arm CT PBV and MR-derived CBV and CBF measurements. RESULTS: All patients received medical management, while eight patients (31%) underwent selective intra-arterial chemical angioplasty. Colour-coded C-arm CT PBV maps were 91% sensitive and 100% specific in detecting the perfusion abnormalities. C-arm CT rPBV demonstrated good agreement and strong correlation with both MR-rCBV and MR-rCBF measurements; the agreement and correlation were stronger for MR-rCBF relative to MR-rCBV and improved for C-arm CT PBV versus the geometric mean of MR-rCBV and MR-rCBF. Analysis of weighted means showed that the C-arm CT PBV has a preferential blood flow weighting (≈ 60% blood flow and ≈ 40% blood volume weighting). CONCLUSIONS: C-arm CT PBV imaging is feasible in DCI following aneurysmal SAH. PBV is a composite perfusion parameter incorporating both blood flow and blood volume weightings. That PBV has preferential (≈ 60%) blood flow weighting is an important finding, which is of clinical significance when interpreting the C-arm CT PBV maps, particularly in the setting of acute brain ischemia.

An approach to the symbolic representation of brain arteriovenous malformations for management and treatment planning.

INTRODUCTION: There is currently no standardised approach to arteriovenous malformation (AVM) reporting. Existing AVM classification systems focuses on angioarchitectural features and omit haemodynamic, anatomical and topological parameters intuitively used by therapists. METHODS: We introduce a symbolic vocabulary to represent the state of an AVM of the brain at different stages of treatment. The vocabulary encompasses the main anatomic and haemodynamic features of interest in treatment planning and provides shorthand symbols to represent the interventions themselves in a schematic representation. RESULTS: The method was presented to 50 neuroradiologists from 14 countries during a workshop and graded 7.34 ± 1.92 out of ten for its usefulness as means of standardising and facilitating communication between clinicians and allowing comparisons between AVM cases. Feedback from the survey was used to revise the method and improve its completeness. For an AVM test case, participants were asked to produce a conventional written report and subsequently a diagrammatic report. The two required, on average, 6.19 ± 2.05 and 5.09 ± 3.01 min, respectively. Eighteen participants said that producing the diagram changed the way they thought about the AVM test case. CONCLUSION: Introduced into routine practice, the diagrams would represent a step towards a standardised approach to AVM reporting with consequent benefits for comparative analysis and communication as well as for identifying best treatment strategies.

Volume changes of extremely large and giant intracranial aneurysms after treatment with flow diverter stents.

INTRODUCTION: This study assessed volume changes of unruptured large and giant aneurysms (greatest diameter >20 mm) after treatment with flow diverter (FD) stents. METHODS: Clinical audit of the cases treated in a single institution, over a 5-year period. Demographic and clinical data were retrospectively collected from the hospital records. Aneurysm volumes were measured by manual outlining at sequential slices using computerised tomography (CT) or magnetic resonance (MR) angiography data. RESULTS: The audit included eight patients (seven females) with eight aneurysms. Four aneurysms involved the cavernous segment of the internal carotid artery (ICA), three the supraclinoid ICA and one the basilar artery. Seven patients presented with signs and symptoms of mass effect and one with seizures. All but one aneurysm was treated with a single FD stent; six aneurysms were also coiled (either before or simultaneously with FD placement). Minimum follow-up time was 6 months (mean 20 months). At follow-up, three aneurysms decreased in size, three were unchanged and two increased. Both aneurysms that increased in size showed persistent endosaccular flow at follow-up MR; in one case, failure was attributed to suboptimal position of the stent; in the other case, it was attributed to persistence of a side branch originating from the aneurysm (similar to the endoleak phenomenon of aortic aneurysms). At follow-up, five aneurysms were completely occluded; none of these increased in volume. CONCLUSION: Complete occlusion of the aneurysms leads, in most cases, to its shrinkage. In cases of late aneurysm growth or regrowth, consideration should be given to possible endoleak as the cause.

Does hypopituitarism recover when macroprolactinomas are treated with cabergoline?

OBJECTIVE: The frequency and the degree of recovery of anterior pituitary hormone deficits in patients with macroprolactinoma responsive to cabergoline are not clear. Our aim was to evaluate pituitary function in these patients with particular reference to an assessment of the possible restoration of pituitary deficits. SUBJECTS AND METHODS: The records of all subjects prospectively presenting to our Department with macroprolactinomas treated with cabergoline over a 2-year period were reviewed. Pituitary function was assessed at diagnosis and, if abnormal, for three consecutive years for the GH, FSH/LH and ACTH axes, and at 3 years for the TSH axis. RESULTS: Twelve patients were included. Severe GH deficiency was found in 83% at diagnosis and did not resolve in any patient at last assessment. Gonadotrophin deficiency was found in 90% at diagnosis and in 50% at last evaluation (showing reversal in 44% of deficient patients, all achieved within 1 year). ACTH deficiency was found in 17% at diagnosis and it did not reverse in any patient at last assessment. TSH deficiency was found in 36% at diagnosis and in 27% at last assessment (reversal in 25% of deficient patients). CONCLUSIONS: In our study, in a group of patients with macroprolactinoma systematically assessed at intervals, pituitary dysfunction in response to cabergoline was found to be mostly irreversible, except for the gonadotroph axis which showed restoration in a subset of subjects following achievement of normoprolactinaemia. It would appear that the reversibility of pituitary axes may be less common than previously thought.

Can we ever stop imaging in surgically treated and radiotherapy-naive patients with non-functioning pituitary adenoma?

BACKGROUND: Non-functioning pituitary adenomas (NFAs) are slow-growing tumours with reported re-growth rates following surgical resection alone of up to 50% at 10 years. Currently, the desired length of follow-up surveillance imaging in un-irradiated patients is unclear. AIM: To clarify the timing of re-growth in patients with NFAs, treated solely by surgery without post-operative pituitary radiotherapy, and also to clarify whether continued imaging is necessary in these patients. METHODS: A case note analysis of all patients who underwent surgery alone for NFA between January 1984 and December 2007 was undertaken. Patients were followed for a minimum of 1 year. Re-growth was diagnosed on the basis of radiological appearances with or without associated manifestations. RESULTS: One hundred and fifty-five patients (94 males, mean age at diagnosis 57.9 (range 18.3-88) years) were included. Twenty-nine were followed up for more than 10 years. The mean follow-up following surgery was 6.1 years (median 4.3 (range 1-25.8)). Re-growth was documented in 54 (34.8%) cases and 20.4% of these cases showed relapse/re-growth 10 or more years after the initial surgery. Kaplan-Meier analysis showed relapse rates of 23.1, 46.7 and 67.9% at 5, 10 and 15 years respectively. There was a significant increase in the re-growth rates if there was either pituitary tumour remnant observed on the first post-operative scan (P≤0.001) or a younger age at initial surgery (P=0.034). CONCLUSION: These results suggest that patients with NFAs need to be closely monitored following surgery, particularly those with post-operative tumour remnants. With 20% of relapse occurring after 10 years, follow-up surveillance needs to be continued beyond this time.

Recurrence of hyperprolactinaemia following discontinuation of dopamine agonist therapy in patients with prolactinoma occurs commonly especially in macroprolactinoma.

CONTEXT: The optimal duration of dopamine agonist (DA) therapy in prolactinoma is unknown. There are concerns that despite low recurrence rates in highly selected groups, high recurrence rates after DA withdrawal may occur in routine practice. OBJECTIVE: To explore recurrence of hyperprolactinaemia and predictive factors following DA withdrawal in patients with microprolactinoma and macroprolactinoma. DESIGN: A retrospective study on adult patients with confirmed prolactinoma attending the Oxford Endocrine Department. PATIENTS AND MEASUREMENTS: We identified patients with macroprolactinoma (n = 15) and microprolactinoma (n = 45) treated with DA therapy for >3 years, with a trial off DA therapy. None had other treatments. Measurements included recurrence of hyperprolactinaemia following DA withdrawal, tumour size (macroprolactinomas), duration of DA therapy, prolactin levels (baseline, during DA therapy, recurrence) and time to recurrence. Data were reported as mean (range). RESULTS: During DA therapy, prolactin levels suppressed to normal range in all patients with macroprolactinoma and microprolactinoma, and most macroprolactinomas (n = 14) had substantial tumour shrinkage. Hyperprolactinaemia recurred in 93% of macroprolactinomas (n = 14) at 8·8 months (3-36) and 64% of microprolactinomas (n = 29) at 4·8 months (3-12). Duration of DA therapy was 7·5 years (4-15) for macroprolactinomas and 4·1 years (3-10) for microprolactinomas. Prolactin levels during DA therapy were 144 mU/l (7-336) for macroprolactinomas and 278 mU/l (30-629) for microprolactinomas. For microprolactinomas, prolactin levels during DA therapy were less suppressed in those with recurrence than in those without recurrence (P < 0·05). CONCLUSIONS: In routine practice, hyperprolactinaemia recurs early in most macroprolactinomas (93%) and microprolactinomas (64%) following DA therapy discontinuation. For most macroprolactinomas, cessation of DA cannot be recommended even after 7 years of therapy.

Sixteen-year single-surgeon experience with coil embolization for ruptured intracranial aneurysms: recurrence rates and incidence of late rebleeding. Clinical article.

OBJECT: Over a 16-year period, 570 patients presenting with acute aneurysmal subarachnoid hemorrhage were successfully treated using endosaccular coil embolization within 30 days of hemorrhage by a single surgeon. Patients were followed to assess the stability of aneurysm occlusion and its longer-term efficacy in protecting against rebleeding. METHODS: Patients were followed for 6 to 191 months (mean 73.7 months, median 67 months) by clinical review, angiography performed at 6 and 24 months posttreatment, and questionnaires sent via the postal service every 5 years. Late rebleeding was defined as > 30 days after treatment. RESULTS: Stable angiographic occlusion was evident in 74.5% of small, 72.2% of large, and 60% of giant aneurysms. Recurrent filling was found in 119 (26.3%) of 452 aneurysms. Rebleeding was diagnosed in 9 patients (6 treated aneurysms) and occurred between 2 and 114 months posttreatment. It was due to aneurysm recurrence in 6 patients, rupture of a coincidental untreated aneurysm in 2 patients, and rupture of a de novo aneurysm in 1 patient. Rebleeding occurred in 3 (2.5%) of 119 unstable aneurysms and in 3 (0.9%) of 333 stable aneurysms, as seen on initial follow-up angiography studies. Annual rebleeding rates ranged from 0.2% to 0.6% for all causes and from 0.2% to 0.4% for rebleeding of treated aneurysms. No rebleeding was recorded after the first decade, with 138 patients having more than 10 years of follow-up. CONCLUSIONS: Periodic follow-up with angiographic studies after coil embolization is recommended to identify aneurysm recurrence and patients at a high risk of late rebleeding in the medium term. More frequent follow-up is recommended for patients harboring coincidental unruptured aneurysms.

Assessment of angiographic outcomes after flow diversion treatment of intracranial aneurysms: a new grading schema.

INTRODUCTION: Flow diverter (FD) devices have emerged as an alternative treatment for a subgroup of intracranial aneurysms. The principle of endovascular flow diversion is inherently different from endosaccular coil embolisation. To monitor the angiographic outcomes for FDs, a sensitive and reliable new measure is required. Oxford Neurovascular and Neuroradiology Research Unit developed a grading schema while conducting a registry to audit outcomes of patients treated using a particular FD (SILK flow diverter; Balt Extrusion, Montmorency, France). The aim of this study is to assess the applicability and reproducibility of the new schema. METHODS: The proposed grading schema is designed for saccular- or fusiform-shaped aneurysms. For both, it documents the degree of aneurysm occlusion using a five-point scale and the parent artery patency on a three-point scale. Two neuroradiologists used the schema to independently rate 55 angiograms showing comparable treatment and follow-up angiograms of patients treated with a FD. Inter-observer agreement was estimated using the weighted kappa co-efficient. RESULTS: Both readers found the schema easy to apply. Overall, there were ten discordant readings for degrees of aneurysm occlusion and two for parent artery patency. Inter-observer agreement was excellent for both the assessment of aneurysm occlusion (k=0.89; C.I.=0.81-0.99) and parent artery patency (k=0.90; C.I.=0.76-1.0). CONCLUSION: The proposed schema is sufficiently sensitive to register gradual aneurysm occlusion and parent artery patency on interval angiograms. It is reproducible and is applicable to both saccular and fusiform aneurysms. More data on follow-up of FD-treated aneurysms is needed to prove its efficacy in predicting the long-term behaviour of treated aneurysms.