A Pragmatic Randomized Trial Comparing Surgical Clipping and Endovascular Treatment of Unruptured Intracranial Aneurysms.

BACKGROUND AND PURPOSE: Surgical clipping and endovascular treatment are commonly used in patients with unruptured intracranial aneurysms. We compared the safety and efficacy of the 2 treatments in a randomized trial. MATERIALS AND METHODS: Clipping or endovascular treatments were randomly allocated to patients with one or more 3- to 25-mm unruptured intracranial aneurysms judged treatable both ways by participating physicians. The study hypothesized that clipping would decrease the incidence of treatment failure from 13% to 4%, a composite primary outcome defined as failure of aneurysm occlusion, intracranial hemorrhage during follow-up, or residual aneurysms at 1 year, as adjudicated by a core lab. Safety outcomes included new neurologic deficits following treatment, hospitalization of >5 days, and overall morbidity and mortality (mRS > 2) at 1 year. There was no blinding. RESULTS: Two hundred ninety-one patients were enrolled from 2010 to 2020 in 7 centers. The 1-year primary outcome, ascertainable in 290/291 (99%) patients, was reached in 13/142 (9%; 95% CI, 5%-15%) patients allocated to surgery and in 28/148 (19%; 95% CI, 13%-26%) patients allocated to endovascular treatments (relative risk: 2.07; 95% CI, 1.12-3.83; P = .021). Morbidity and mortality (mRS >2) at 1 year occurred in 3/143 and 3/148 (2%; 95% CI, 1%-6%) patients allocated to surgery and endovascular treatments, respectively. Neurologic deficits (32/143, 22%; 95% CI, 16%-30% versus 19/148, 12%; 95% CI, 8%-19%; relative risk: 1.74; 95% CI, 1.04-2.92; P = .04) and hospitalizations beyond 5 days (69/143, 48%; 95% CI, 40%-56% versus 12/148, 8%; 95% CI, 5%-14%; relative risk: 0.18; 95% CI, 0.11-0.31; P < .001) were more frequent after surgery. CONCLUSIONS: Surgical clipping is more effective than endovascular treatment of unruptured intracranial aneurysms in terms of the frequency of the primary outcome of treatment failure. Results were mainly driven by angiographic results at 1 year.

Douglas Altman's 2009 Grand Lecture: Can we trust our literature?

Recent studies of the medical literature have revealed numerous and serious problems. Errors in the design, methods and interpretation of studies can frequently be identified. A huge hidden problem is publication bias, the tendency for positive articles to be published, while negative articles are either not written or submitted. This can systematically lead to an overestimation of the value of treatments, of diagnostic or prognostic studies. Even more worrisome is selective reporting: only a subset of a wide array of tested hypotheses are presented (the ones that turned out to be positive with significance testing). This is particularly true for secondary endpoints and subgroup findings, but even the primary endpoints of trials have been modified when publications are compared to protocols. The peer-review process is fallible. Even if it were strengthened, reviewers cannot examine what is not reported. Hence many problems can only be mitigated with better reporting. Numerous initiatives have proposed guidelines to promote transparent reporting, but progress is slow.

Noninvasive Angiographic Results of Clipped or Coiled Intracranial Aneurysms: An Inter- and Intraobserver Reliability Study.

BACKGROUND AND PURPOSE: Noninvasive angiography is commonly used to assess the outcome of surgical or endovascular treatment of intracranial aneurysms in clinical series or randomized trials. We sought to assess whether a standardized 3-grade classification system could be reliably used to compare the CTA and MRA results of both treatments. MATERIALS AND METHODS: An electronic portfolio composed of CTAs of 30 clipped and MRAs of 30 coiled aneurysms was independently evaluated by 24 raters of diverse experience and training backgrounds. Twenty raters performed a second evaluation 1 month later. Raters were asked which angiographic grade and management decision (retreatment; close or long-term follow-up) would be most appropriate for each case. Agreement was analyzed using the Krippendorff α (αK) statistic, and the relationship between angiographic grade and clinical management choice, using the Fisher exact and Cramer V tests. RESULTS: Interrater agreement was substantial (αK = 0.63; 95% CI, 0.55-0.70); results were slightly better for MRA results of coiling (αK = 0.69; 95% CI, 0.56-0.76) than for CTA results of clipping (αK = 0.58; 95% CI, 0.44-0.69). Intrarater agreement was substantial to almost perfect. Interrater agreement regarding clinical management was moderate for both clipped (αK = 0.49; 95% CI, 0.32-0.61) and coiled subgroups (αK = 0.47; 95% CI, 0.34-0.54). The choice of clinical management was strongly associated with the size of the residuum (mean Cramer V = 0.77 [SD, 0.14]), but complete occlusions (grade 1) were followed more closely after coiling than after clipping (P = .01). CONCLUSIONS: A standardized 3-grade scale was found to be a reliable and clinically meaningful tool to compare the results of clipping and coiling of aneurysms using CTA or MRA.

Reliability of CT Angiography in Cerebral Vasospasm: A Systematic Review of the Literature and an Inter- and Intraobserver Study.

BACKGROUND AND PURPOSE: Computed tomography angiography offers a non-invasive alternative to DSA for the assessment of cerebral vasospasm following subarachnoid hemorrhage but there is limited evidence regarding its reliability. Our aim was to perform a systematic review (Part I) and to assess (Part II) the inter- and intraobserver reliability of CTA in the diagnosis of cerebral vasospasm. MATERIALS AND METHODS: In Part I, articles reporting the reliability of CTA up to May 2018 were systematically searched and evaluated. In Part II, 11 raters independently graded 17 arterial segments in each of 50 patients with SAH for the presence of vasospasm using a 4-category scale. Raters were additionally asked to judge the presence of any moderate/severe vasospasm (≥ 50% narrowing) and whether findings would justify augmentation of medical treatment or conventional angiography ± balloon angioplasty. Four raters took part in the intraobserver reliability study. RESULTS: In Part I, the systematic review revealed few studies with heterogeneous vasospasm definitions. In Part II, we found interrater reliability to be moderate at best (κ ≤ 0.6), even when results were stratified according to specialty and experience. Intrarater reliability was substantial (κ > 0.6) in 3/4 readers. In the per arterial segment analysis, substantial agreement was reached only for the middle cerebral arteries, and only when senior raters' judgments were dichotomized (presence or absence of ≥50% narrowing). Agreement on the medical or angiographic management of vasospasm based on CTA alone was less than substantial (κ ≤ 0.6). CONCLUSIONS: The diagnosis of vasospasm using CTA alone was not sufficiently repeatable among observers to support its general use to guide decisions in the clinical management of patients with SAH.

A randomized trial of endovascular versus surgical management of ruptured intracranial aneurysms: Interim results from ISAT2.

BACKGROUND AND PURPOSE: Appropriate management of ruptured intracranial aneurysm (RIA) in patients eligible for surgical clipping but under-represented in or excluded from previous randomized trials remains undetermined. METHODS: The International Subarachnoid Aneurysm Trial-2 (ISAT-2) is a randomized care trial comparing surgical versus endovascular treatment (EVT) of RIA. All patients considered for surgical clipping but eligible for endovascular treatment can be included. The primary endpoint is death or dependency on modified Rankin score (mRS>2) at 1 year. Secondary endpoints are 1 year angiographic results and length of hospital stay. RESULTS: An interim analysis was performed after 103 patients were treated from November 2012 to July 2017 in 4 active centers. Fifty-two of the 55 patients allocated to surgery were treated by clipping, and 45 of the 48 allocated to EVT were treated by coiling, with 3 crossovers in each arm. The main endpoint (1 year mRS>2), available for 76 patients, was reached in 16/42 patients allocated to clipping (38%; 95%CI: 25%-53%), and 10/34 patients allocated to coiling (29%; 17%-46%). One year imaging results were available in 54 patients: complete aneurysm occlusion was found in 23/27 patients allocated to clipping (85%; 67%-94%), and 18/27 patients allocated to coiling (67%; 47%-81%). Hospital stay exceeding 20 days was more frequent in surgery (26/55 [47%; 34%-60%]) than EVT (9/48 [19%; 10%-31%]). CONCLUSION: Ruptured aneurysm patients for whom surgical clipping may still be best can be managed in a randomized care trial, which is feasible in some centers. More participating centers are needed.

Hydrogel versus Bare Platinum Coils in Patients with Large or Recurrent Aneurysms Prone to Recurrence after Endovascular Treatment: A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Some patients are at high risk of aneurysm recurrence after endovascular treatment: patients with large aneurysms (Patients Prone to Recurrence After Endovascular Treatment PRET-1) or with aneurysms that have previously recurred after coiling (PRET-2). We aimed to establish whether the use of hydrogel coils improved efficacy outcomes compared with bare platinum coils. MATERIALS AND METHODS: PRET was an investigator-led, pragmatic, multicenter, parallel, randomized (1:1) trial. Randomized allocation was performed separately for patients in PRET-1 and PRET-2, by using a Web-based platform ensuring concealed allocation. The primary outcome was a composite of a residual/recurrent aneurysm, adjudicated by a blinded core laboratory, or retreatment, intracranial bleeding, or mass effect during the 18-month follow-up. Secondary outcomes included adverse events, mortality, and morbidity (mRS > 2). The hypothesis was that hydrogel would decrease the primary outcome from 50% to 30% at 18 months, necessitating 125 patients per group (500 for PRET-1 and PRET-2). RESULTS: The trial was stopped once 250 patients in PRET-1 and 197 in PRET-2 had been recruited because of slow accrual. A poor primary outcome occurred in 44.4% (95% CI, 35.5%-53.2%) of those in PRET-1 allocated to platinum compared with 52.5% (95% CI, 43.4%-61.6%) of patients allocated to hydrogel (OR, 1.387; 95% CI, 0.838-2.295; P = .20) and in 49.0% (95% CI, 38.8%-59.1%) in PRET-2 allocated to platinum compared with 42.1% (95% CI, 32.0%-52.2%) allocated to hydrogel (OR, 0.959; 95% CI, 0.428-1.342; P = .34). Adverse events and morbidity were similar. There were 3.6% deaths (1.4% platinum, 5.9% hydrogel; P = .011). CONCLUSIONS: Coiling of large and recurrent aneurysms is safe but often poorly effective according to angiographic results. Hydrogel coiling was not shown to be better than platinum.

Agreement studies in radiology research.

PURPOSE: The goal of this study was to estimate the frequency and the quality of agreement studies published in diagnostic imaging journals. MATERIALS AND METHODS: All studies published between January 2011 and December 2012 in four radiology journals were reviewed. Four trained readers evaluated agreement studies using a 24-item form that included the 15 items of the Guidelines for Reporting Reliability and Agreement Studies criteria. RESULTS: Of 2229 source titles, 280 studies (13%) reported agreement. The mean number of patients per study was 81±99 (SD) (range, 0-180). Justification for sample size was found in 9 studies (3%). The number of raters was≤2 in 226 studies (81%). No intra-observer study was performed in 212 (76%) articles. Confidence intervals and interpretation of statistical estimates were provided in 98 (35%) and 147 (53%) of the studies, respectively. In 168 studies (60%), the agreement study was not mentioned in the discussion section. In 8 studies (3%), reporting of the agreement study was judged to be adequate. Twenty studies (7%) were dedicated to agreement. CONCLUSION: Agreement studies are preliminary and not adequately reported. Studies dedicated to agreement are infrequent. They are research opportunities that should be promoted.

Interobserver agreement in the interpretation of outpatient head CT scans in an academic neuroradiology practice.

BACKGROUND AND PURPOSE: The repeatability of head CT interpretations may be studied in different contexts: in peer-review quality assurance interventions or in interobserver agreement studies. We assessed the agreement between double-blind reports of outpatient CT scans in a routine academic practice. MATERIALS AND METHODS: Outpatient head CT scans (119 patients) were randomly selected to be read twice in a blinded fashion by 8 neuroradiologists practicing in an academic institution during 1 year. Nonstandardized reports were analyzed to extract 4 items (answer to the clinical question, major findings, incidental findings, recommendations for further investigations) from each report, to identify agreement or discrepancies (classified as class 2 [mentioned or not mentioned or contradictions between reports], class 1 [mentioned in both reports but diverging in location or severity], 0 [concordant], or not applicable), according to a standardized data-extraction form. Agreement regarding the presence or absence of clinically significant or incidental findings was studied with κ statistics. RESULTS: The interobserver agreement regarding head CT studies with positive and negative results for clinically pertinent findings was 0.86 (0.77-0.95), but concordance was only 75.6% (67.2%-82.5%). Class 2 discrepancy was found in 15.1%; class 1 discrepancy, in 9.2% of cases. The κ value for reporting incidental findings was 0.59 (0.45-0.74), with class 2 discrepancy in 29.4% of cases. Most discrepancies did not impact the clinical management of patients. CONCLUSIONS: Discrepancies in double-blind interpretations of head CT examinations were more common than reported in peer-review quality assurance programs.

Patients prone to recurrence after endovascular treatment: periprocedural results of the PRET randomized trial on large and recurrent aneurysms.

BACKGROUND AND PURPOSE: Some patients with large or recurrent aneurysms may be at increased risk of recurrence postcoiling. The Patients Prone to Recurrence after Endovascular Treatment (PRET) trial was designed to assess whether hydrogel coils were superior to platinum coils in these high-risk patients. This article reports periprocedural safety and operator-assessed angiographic results from the PRET trial. MATERIALS AND METHODS: PRET was a pragmatic, multicenter, randomized controlled trial. Patients had ≥10-mm aneurysms (PRET-1) or a major recurrence after coiling of an aneurysm of any size (PRET-2). Patients were randomly allocated to hydrogel or control arms (any platinum coil) by using concealed allocation with minimization. Assist devices could be used as clinically required. Aneurysms could be unruptured or recently ruptured. Analyses were on an intent-to-treat basis. RESULTS: Four hundred forty-seven patients were recruited (250 PRET-1; 197 PRET-2). Aneurysms were recently ruptured in 29% of PRET-1 and 4% of PRET-2 patients. Aneurysms were ≥10 mm in all PRET-1 and in 50% of PRET-2 patients. They were wide-neck (≥4 mm) in 70% and in the posterior circulation in 24% of patients. Stents were used in 28% of patients (35% in PRET-2). Coiling was successful in 98%. Adverse events occurred in 28 patients with hydrogel and 23 with platinum coils. Mortality (n=2, unrelated to treatment) and morbidity (defined as mRS>2 at 1 month) occurred in 25 patients (5.6%; 12 hydrogel, 13 platinum), related to treatment in 10 (4 hydrogel; 6 platinum) (or 2.3% of 444 treated patients). No difference was seen between hydrogel and platinum for any of the indices used to assess safety up to at least 30 days after treatment. At 1 month, 95% of patients were home with a good outcome (mRS≤2 or unchanged). Operator-assessed angiographic outcomes were satisfactory (complete occlusion or residual neck) in 339 of 447 or 76.4% of patients, with no significant difference between groups. CONCLUSIONS: Endovascular treatment of large and recurrent aneurysms can be performed safely with platinum or hydrogel coils.

Structural abnormalities in patients with insular/peri-insular epilepsy: spectrum, frequency, and pharmacoresistance.

SUMMARY: Between 2002 and 2010, a total of 48 patients were seen at our epilepsy clinic with insular/peri-insular cortex epilepsy. Review of their MR imaging scans revealed a neoplastic lesion in 27% of patients, a malformation of cortical development in 21%, a vascular malformation in 19%, and atrophy/gliosis from an acquired insult in 17%. MR imaging results were normal in 4 patients. Other miscellaneous findings included a case of Rasmussen encephalitis, a nonspecific insular millimetric T2 signal abnormality, a neuroepithelial cyst, and hippocampal sclerosis without MR imaging evidence of dual insular pathologic features (despite depth electrode-proven insular seizures). Refractoriness to antiepileptic drug treatment was present in 56% of patients: 100% for patients with malformations of cortical development (1.0; 95% CI, 0.72-1.0), 50.0% (0.5; 95% CI, 0.21-0.78) in the presence of atrophy/gliosis from acquired insults, 39% (0.39; 95% CI, 0.14-0.68) for neoplastic lesions, and 22.2% (0.22; 95% CI, 0.06-0.55) for vascular malformations.

Liquid embolization material reduces the delivered radiation dose: clinical myth or reality?

BACKGROUND AND PURPOSE: To be radiopaque, BAVM embolization products must contain high-atomic-number materials, which may also attenuate photon beams delivered with radiosurgery. This "shielding effect" has been invoked to explain why radiation therapy may be less effective for previously embolized BAVMs. To evaluate the impact of embolization material on radiation dose, we measured and compared the dose delivered to the center of an AVM model, before and following embolization with various materials in a LINAC. MATERIALS AND METHODS: Two in vitro AVM models were constructed by drilling interconnected tubular perforations in plastic water phantoms to simulate nidal vessels. Phantoms were designed to allow the positioning of a radiation detector at their center. One model was embolized with Onyx 18 and a second model, with a combination of Indermil, Lipiodol, tungsten powder, and Onyx 18. The radiation delivered was compared between embolized and nonembolized controls following irradiation with a standard 250-cGy dose. RESULTS: The mean dose of radiation delivered to the model embolized with Onyx alone was 244 ± 5 cGy before and 246 ± 5 cGy following embolization. The mean dose of radiation delivered to the model embolized with various agents was 242 ± 5 cGy before, and 254 ± 5 cGy after embolization. CONCLUSIONS: Embolic material did not reduce the radiation dose delivered by a LINAC to the center of our experimental BAVM models. The shielding effect may be compensated by scattered and reflected radiation.

Outcomes of endovascular treatments of aneurysms: observer variability and implications for interpreting case series and planning randomized trials.

BACKGROUND AND PURPOSE: Angiographic results are commonly used as a surrogate marker of success of coiling of intracranial aneurysms. Inter- and intraobserver agreement in judging angiographic results remain poorly characterized. Our goal was to offer such an evaluation of a grading scale commonly used to evaluate results of endovascular treatment of aneurysms. MATERIALS AND METHODS: A portfolio of 90 angiographic images from 45 patients selected from the core lab data base of a randomized trial was sent to 12 observers on 2 occasions more than 3 months apart. The variability of a 3-value grading scale used to score angiographic results and of a final judgment regarding the presence of a recurrence was studied using κ statistics. RESULTS: Ten participants responded once and 6 responded twice. Agreement was poor to moderate (κ = 0.28-0.5) for senior and junior observers judging angiographic results immediately or 12-18 months after treatment. Agreement reached a reassuring "substantial" (κ = 0.62) level, with a dichotomous presence-absence of a major recurrence, and intraobserver agreement was better in experienced core lab assessors. CONCLUSIONS: There is an important variability in the assessment of angiographic outcomes of endovascular treatments, rendering comparisons between publications risky, if not invalid. A simple dichotomous judgment can be used as a surrogate outcome in randomized trials designed to assess the value of new endovascular devices.

Flow diversion in aneurysms trial: the design of the FIAT study.

Intracranial aneurysms, particularly large and giant, fusiform or recurrent aneurysms are increasingly treated with flow diverters (FDs), a recently introduced and approved neurovascular device. While some rare cases may not be treated any other way, in most patients a more conventional, conservative, or validated approach such as coiling, parent vessel occlusion, or surgical clipping exists. Only a randomized clinical trial can answer the question of which treatment option leads to better patient outcomes.We report the design of the FIAT study, a clinical care trial aiming to compare angiographic and clinical outcomes following treatment with a Flow-Diverter or with the best conventional treatment option. The FIAT study will include both a randomized and a registry portion. Patients will be proposed randomization to either FD stenting or best conventional treatment option (observation, coiling, stenting, or clipping) as determined by the treating physician. FIAT will recruit a total of 338 patients, to show that i) FD stenting can be performed with an 'acceptable' immediate complication rate of less than 15% morbidity and mortality (defined as mRS > 2); ii) FD stenting can increase from 75 to 90% the proportion of patients with a "good outcome", defined as complete or near-complete occlusion of the aneurysm AND a good clinical outcome (mRS ≥ 2) at one year, as compared to the best conventional option. The FIAT study provides a scientific and ethical context to care for patients eligible for flow-diversion therapy.

Transformation of a cranial fusiform aneurysm into a pseudotumoral-like mass prior to spontaneous occlusion and regression.

This report documents the evolution of a non-ruptured cranial fusiform aneurysm that underwent both spontaneous occlusion and regression. During this process, unique images of the aneurysm as a pseudotumoral-like mass were obtained. The pseudotumoral-like mass most likely reflected inflammation and secondary neovascularization within the aneurysm, supporting the theory that spontaneous aneurysmal healing involves an inflammatory process.

Assessing prognosis from nonrandomized studies: an example from brain arteriovenous malformations.

Two recent publications from Helsinki and Toronto that investigated the natural history of brain AVMs are the background topic for reviewing some principles and pitfalls of prognostic studies. Multivariable prognostic research involves 3 steps: developing the prognostic model, validating its performance in other individuals, and assessing its clinical impact on patients' outcomes. Unfortunately, the predictive ability of the model can be poor when it is applied to a new population, and clinical impact studies are rarely performed. Models that have not been validated should not be used to inform clinical decisions. Unfortunately, for rare outcomes in rare diseases, clinical data are limited. Although the 2 studies on brain AVMs may represent the best data currently available, they still included few patients with events and there are several methodologic concerns undermining the reliability of results. The estimates of risk of rupture per year are uncertain. Multiplying those uncertain numbers by the life expectancy of individuals can inflate error beyond control. Hence relying on these estimates to make clinical decisions may be dangerous.

The problem of subgroup analyses: an example from a trial on ruptured intracranial aneurysms.

The randomized ISAT demonstrated the superiority of endovascular treatment in patients with ruptured intracranial aneurysms considered suitable for either clipping or coiling. A later publication proposed a second look at the results, demonstrating that older patients with ruptured MCA aneurysms appeared to benefit from clipping, in disagreement with the general findings of the trial. Subgroup analyses in randomized trials and observational studies examine whether effects of interventions differ between subgroups according to the characteristics of patients. However, many apparent subgroup effects have been shown to be spurious. Misleading subgroup effects can result in withholding efficacious treatment from patients who would benefit or can encourage ineffective or potentially harmful treatments for patients who would fare better without. Some guidelines for the prudent interpretation of subgroup findings are reviewed.

Analysis by categorizing or dichotomizing continuous variables is inadvisable: an example from the natural history of unruptured aneurysms.

In medical research analyses, continuous variables are often converted into categoric variables by grouping values into ≥2 categories. The simplicity achieved by creating ≥2 artificial groups has a cost: Grouping may create rather than avoid problems. In particular, dichotomization leads to a considerable loss of power and incomplete correction for confounding factors. The use of data-derived "optimal" cut-points can lead to serious bias and should at least be tested on independent observations to assess their validity. Both problems are illustrated by the way the results of a registry on unruptured intracranial aneurysms are commonly used. Extreme caution should restrict the application of such results to clinical decision-making. Categorization of continuous data, especially dichotomization, is unnecessary for statistical analysis. Continuous explanatory variables should be left alone in statistical models.

Endovascular parent artery occlusion for the treatment of wide-neck A1 segment aneurysms: a single-center experience.

The goal of this study was to evaluate the feasibility and efficacy of A1 occlusion at the level of wide necked A1 aneurysms, where there are bilateral patent A1 segments and a patent AcomA. Between 2000 and 2010, 9 patients with wide necked A1 aneurysms were treated by coiling of the aneurysm along with parent vessel occlusion. All aneurysms had a wide neck (≥ 4 mm). None were treated in the acute phase of a subarachnoid hemorrhage. Three small infarcts were noted on routine post-treatment head CT, 1 of which was symptomatic (transient hemiparesthesia). On control angiogram at 6 months or more, 3 A1 recanalizations were found, 2 of which had a stable small neck recurrence. None of the aneurysms ruptured on follow-up. In this series, parent artery occlusion was effective in treating wide-necked aneurysms arising from the A1 segment in patients with adequate collateral supply.

A new canine carotid artery bifurcation aneurysm model for the evaluation of neurovascular devices.

BACKGROUND AND PURPOSE: Stents are increasingly used for coiling of difficult aneurysms, to reduce the risk of recurrences, or to modify blood flow. Currently available bifurcation aneurysm models are ill-suited to assess stent performance before clinical use. We designed a new wide-neck canine T-type bifurcation aneurysm model. Its potential value as a training tool as well as in the evaluation of new techniques or embolic agents was assessed. Our first task was to verify that recurrences occurred after satisfactory coiling. A second aim of this preliminary work was to assess if the new model could recreate the technical challenges involved in bifurcation aneurysms. MATERIALS AND METHODS: We introduce a new canine wide-neck bifurcation aneurysm model, created by using a vein pouch at the apex of an end-to-side anastomosis of the carotid arteries, with flow reversal in the proximal RCA by ligation of the innominate artery. Three aneurysms were treated with coil embolization, 10 were treated with stents (7 self-expandable, 3 balloon-expandable), and 3 were left untreated. Aneurysms were followed by duplex ultrasonography and angiography, and studied with macroscopic photography after euthanasia 11.8 +/- 3.9 months after surgery. RESULTS: All aneurysms remained patent at 9.0 +/- 3.6 months' follow-up. Coiling led to recurrences by 3 months in all 3 cases. Stent placement was technically difficult in all cases and did not lead to aneurysm thrombosis or neointimal closure of the aneurysm neck at 3 months. CONCLUSIONS: This model may be suitable for studying the effects of endovascular treatment on aneurysm and branch occlusion rates, for preclinical testing of stents and other intravascular devices, and for training students of endovascular technique.

Unruptured intracranial aneurysms: their illusive natural history and why subgroup statistics cannot provide normative criteria for clinical decisions or selection criteria for a randomized trial.

There is currently no evidence that treatment of unruptured aneurysms is beneficial. Confronted with the uncertainty, many clinicians are attracted by an individual calculus of risks using numbers extracted from subgroup statistics of observational studies or natural history data. The so-called natural history of unruptured aneurysms refers to a purely man-made ratio of events divided by the number of untreated patients identified by imaging, a ratio heavily influenced by referral patterns and arbitrary clinical decisions. Available studies lacked prespecified hypotheses, exposing all analyses to sampling error and bias, and sample sizes were too small to provide reliable subgroup statistics. Far from being "natural kinds" of aneurysms, subgroups were post-hoc creations. Resulting data-driven statistics can only be exploratory, the error too uncontrollable to serve for clinical decisions. A randomized trial is in order, but selection according to fixed size criteria is ill-advised, given the imprecision of imaging, the influence of other factors such as location, previous history, multiplicity of lesions, risks of treatment, age and the danger of arbitrarily excluding from a long trial a large segment of the population with aneurysms for whom the research question is most pertinent.