Effects of circle of Willis anatomic variations on angiographic and clinical outcomes of coiled anterior communicating artery aneurysms.

BACKGROUND AND PURPOSE: Anterior communicating artery aneurysms account for one-fourth of all intracranial aneurysms and frequently occur in the context of A1 vessel asymmetry. The purpose of this study was to correlate circle of Willis anatomic variation association to angiographic and clinical outcomes of anterior communicating aneurysm coiling. MATERIALS AND METHODS: The Cerecyte Coil Trial provides a subgroup of 124 cases with anterior communicating artery aneurysms after endovascular coiling. One hundred seventeen of 124 anterior communicating artery aneurysms had complete imaging and follow-up for clinical outcome analysis, stability of aneurysm coil packing, and follow-up imaging between 5 and 7 months after treatment. Clinical outcomes were assessed by the mRS at 6 months. RESULTS: Anterior cerebral artery trunk-dominance was seen in 91 of 124 (73%) anterior communicating artery aneurysms and codominance in 33 of 124 (27%) anterior communicating artery aneurysms. There was no significant difference (P > .5) in treatment success at 5-7 months for anterior communicating artery aneurysms between the anterior cerebral artery trunk-dominant (49 of 86, 57%) and anterior cerebral artery trunk-codominant (19 of 31) groups. Angiographic follow-up demonstrates a statistically significant increase in neck remnants and progressive aneurysm sac filling with the A1 dominant configuration (n = 21, 24% at follow-up versus n = 11, 12% at immediate posttreatment, P = .035). There was no statistically significant difference in clinical outcomes between types of anterior cerebral artery trunk configuration (P > .5). CONCLUSIONS: Anterior communicating artery aneurysms with anterior cerebral artery trunk-dominant circle of Willis configurations show less angiographic stability at follow-up than those with anterior cerebral artery trunk-codominance similar to other "termination" type aneurysms. This supports the hypothesis that anterior cerebral artery trunk-dominant flow contributes to aneurysm formation, growth, and instability after coiling treatment.

Endovascular treatment of 300 consecutive middle cerebral artery aneurysms: clinical and radiologic outcomes.

BACKGROUND AND PURPOSE: There is controversy as to the best mode of treating MCA aneurysms. We report the results of a large endovascular series of patients treated at our center. MATERIALS AND METHODS: This study was a retrospective analysis of a prospectively acquired data base. All patients with saccular MCA aneurysms treated between November 1996 and June 2012 were included. World Federation of Neurosurgical Societies grade, aneurysm site, size, and aneurysm neck size were recorded, along with clinical outcome assessed with the Glasgow Outcome Scale and radiographic occlusion assessed with the Raymond classification at 6 months and 2.5 years. RESULTS: A total of 295 patients with 300 MCA aneurysms were treated including 244 ruptured aneurysms (80.7%). The technical failure rate was 4.3% (13 patients). Complete occlusion or neck remnant was achieved in 264 (91.4%). Complications included rupture in 15 patients (5%), thromboembolism in 17 patients (5.7%), and early rebleeding in 3 patients (1%). Overall permanent procedural-related morbidity and mortality were seen in 12 patients (7.8%). Of the ruptured aneurysms, 189 (79.4%) had a favorable clinical outcome (Glasgow Outcome Scale score, 4-5). A total of 33 patients (13.6%) died. On initial angiographic follow-up, aneurysm remnant was seen in 18 aneurysms (8.1%). A total of 13 patients (4.3%) were re-treated. CONCLUSIONS: Our experience demonstrates that endovascular treatment of MCA aneurysms has an acceptable safety profile with low rates of technical failure and re-treatment. Therefore, coiling is acceptable as the primary treatment of MCA aneurysms.

Differences in the angiographic evaluation of coiled cerebral aneurysms between a core laboratory reader and operators: results of the Cerecyte Coil Trial.

BACKGROUND AND PURPOSE: Independent evaluation of angiographic images is becoming widely applied in the assessment of treatment outcomes of cerebral aneurysms. In the current study, we assessed the agreement between an independent core laboratory and the operators regarding angiographic appearance in a recent randomized, controlled trial. MATERIALS AND METHODS: Data were derived from the Cerecyte Coil Trial. Angiographic images of each coiled aneurysm, taken immediately after embolization and at 5- to 7-month follow-up, were evaluated by the operator at the treating center and by an independent neuroradiologist at the core laboratory. For the purpose of this study, images were interpreted on a 3-point scale to provide uniformity for analysis; grade 1: complete occlusion, grade 2: neck remnant; and grade 3: sac filling. "Unfavorable angiographic appearance" was defined as grade 3 at follow-up or interval worsening of grade between the 2 time points. RESULTS: The study included 434 aneurysms. Immediately after embolization, grade 3 was reported by operators in 39 (9%) compared with 52 (12%) by the core laboratory (P = .159). On follow-up, grade 3 was reported by operators in 44 (10%) compared with 81 (19%) by the core laboratory (P < .0001). Overall, operators noted unfavorable angiographic appearance in 78 (18%) compared with 134 (31%) by the core laboratory (P < .0001). At every time point, agreement between the core laboratory and the operators was slight. CONCLUSIONS: Unfavorable angiographic appearance was noted almost twice as frequently by an independent core laboratory as compared with the operators. Planning of trials and interpretation of published studies should be done with careful attention to the mode of angiographic appearance interpretation.

Ruptured aneurysms and the International Subarachnoid Aneurysm Trial (ISAT): What is known and what remains to be questioned.

BACKGROUND AND PURPOSE: The International Subarachnoid Aneurysm Trial (ISAT) was a major study comparing clipping and coiling of ruptured intracranial aneurysms. The trial provided answers that were the subject of multiple letters and editorial comments. METHODS: We review the most common critiques that were published in major neurosurgical journals, trying to identify what aspects of ISAT could have been improved, and what questions remain to be studied. RESULTS: Frequent critiques include imprecise selection criteria, lack of requirement for the technical proficiency of surgical participants, lack of angiographic controls of surgically treated patients, and poorly chosen primary endpoints. Other issues that are often raised are the poor recruitment rate which endangered generalization of results, the excessive delays in performing clipping which led to rebleeding episodes, lack of blinding in the assessment of outcomes, and subjective questionnaires. Nonetheless, the design of the study as a pragmatic trial was appropriate, as was the choice of the primary endpoint. The overall trial results could not be verified for all subgroups of interest, and currently many patients who would not have been included in ISAT are treated by coiling, while other patients are treated by clipping despite ISAT results. Hence a new trial, complementary to the original ISAT, may now be indicated. CONCLUSION: ISAT was well-designed and conducted, but many questions remain. They should be addressed by a new trial.

Endovascular stroke treatment today.

The purpose of this study was to review current treatment options in acute ischemic stroke, focusing on the latest advances in the field of mechanical recanalization. These devices recently made available for endovascular intracranial thrombectomy show great potential in acute stroke treatments. Compelling evidence of their recanalization efficacy comes from current mechanical embolectomy trials. In addition to allowing an extension of the therapeutic time window, mechanical recanalization devices can be used without adjuvant thrombolytic therapy, thus diminishing the intracranial bleeding risk. Therefore, these devices are particularly suitable in patients in whom thrombolytic therapy is contraindicated. IV and IA thrombolysis and bridging therapy are viable options in acute stroke treatment. Mechanical recanalization devices can potentially have a clinically relevant impact in the interventional treatment of stroke, but at the present time, a randomized study would be beneficial.

Endovascular coiling in 131 patients with low complication rate justifies treating most unruptured intracranial aneurysms.

BACKGROUND: The management of unruptured intracranial aneurysms (UIAs) remains controversial. The International Study of UIAs (ISUIA) found low rates of rupture and appreciable treatment risks. This finding could be interpreted as suggesting that many UIAs should not be treated. Coiling technology has continuously improved over the years and, since the publication of the International Subarachnoid Aneurysm Trial results, increasing numbers of aneurysms have been coiled, and neurointerventional skills have significantly improved. We present the results of endovascular coiling of 131 patients with UIAs from a high volume unit and a risk-benefit analysis based on patient and aneurysm characteristics. PATIENTS AND METHODS: From December 1996 to September 2005, 131 patients (93 women and 38 men, mean age 51 years) with 151 UIAs were treated using detachable coil embolisation. Data on procedural complications, patient and aneurysm characteristics, clinical and radiological follow up were entered into a prospectively collected database. A risk-benefit analysis was performed. FINDINGS: Endovascular treatment was successful in 145 (96 %) aneurysms. One aneurysm ruptured intraoperatively with a fatal outcome. Ten thromboembolic events occurred, leaving one patient moderately disabled. The combined morbidity and mortality rate per patient at 6 months is 1.5 % (95 % confidence interval: 0.07 - 5.7 %). A risk-benefit analysis comparing these data with the published natural history suggests that treatment with low complication rates can be offered to most patients with UIAs. CONCLUSION: UIAs can be coiled with low morbidity and mortality. The risk-benefit analysis suggests that it is reasonable to off er treatment to patients with the exception of patients over 60 years of age with incidentally found aneurysms less than 7 mm in diameter of the anterior circulation.

Prediction of 60 day case-fatality after aneurysmal subarachnoid haemorrhage: results from the International Subarachnoid Aneurysm Trial (ISAT).

Aneurysmal subarachnoid haemorrhage (aSAH) is a devastating event with substantial case-fatality. Our purpose was to examine which clinical and neuro-imaging characteristics, available on admission, predict 60 day case-fatality in aSAH and to evaluate performance of our prediction model. We performed a secondary analysis of patients enrolled in the International Subarachnoid Aneurysm Trial (ISAT), a randomised multicentre trial to compare coiling with clipping in aSAH patients. Multivariable logistic regression analysis was used to develop a prognostic model to estimate the risk of dying within 60 days from aSAH based on clinical and neuro-imaging characteristics. The model was internally validated with bootstrapping techniques. The study population comprised of 2,128 patients who had been randomised to either endovascular coiling or neurosurgical clipping. In this population 153 patients (7.2%) died within 60 days. World Federation of Neurosurgical Societies (WFNS) grade was the most important predictor of case-fatality, followed by age, lumen size of the aneurysm and Fisher grade. The model discriminated reasonably between those who died within 60 days and those who survived (c statistic = 0.73), with minor optimism according to bootstrap re-sampling (optimism corrected c statistic = 0.70). Several strong predictors are available to predict 60 day case-fatality in aSAH patients who survived the early stage up till a treatment decision; after external validation these predictors could eventually be used in clinical decision making.

Dangerous advances in measurements from digital subtraction angiography: when is a millimeter not a millimeter?

Aneurysms need accurate millimeters (mm). Direct millimeters were lost with digital subtraction angiography (DSA) years ago, with measurements in pixels. Advances in DSA can now give inherent millimeters. The Cerecyte aneurysm coiling trial's angiographic core lab assesses images from compact disc (CD). External fiducials for millimeter calibration are required. Of 25 cases with two 10 mm fiducials, near and far from the intensifier, the midline mean is between 9 "mm" to 15 "mm". Yet 10 mm must be 10 mm. This variance is potentially dangerous. Proprietary software seems to prohibit calibration transfer via CD to another vendor's system.

Detachable coil embolisation of ruptured intracranial aneurysms: a single center study, a decade experience.

OBJECTIVE: The introduction of detachable coils revolutionised the management of patients with intracranial aneurysms and is now considered a first-line treatment in our institution. The purpose of this study was to review 10 years of experience with this method. METHODS: A retrospective review of prospectively collected data on 711 patients undergoing endovascular treatment of ruptured intracranial aneurysm between 1996 and 2005 with regard to technical feasibility, procedural complications, rebleeding, anatomical outcome, need for retreatment and overall clinical outcome. RESULTS: Endovascular treatment failed in 25 aneurysms from a total of 717 (4%). Aneurysm rupture complicated 37 procedures (4.7%) leaving 10 patients permanently disabled or dead (1.3%). Thromboembolic events complicated 35 procedures (4.5%) leaving 8 patients permanently disabled or dead (1%). One other patient died because of fatal parent vessel rupture. Further 6 procedures were complicated by arterial dissection and 18 by coil loop protrusion, however all of these patients achieved independent recovery. Overall morbidity-mortality was 2.9%. Further subarachnoid hemorrhage occurred in 16 patients (2.3%), 12 of which died. Altogether, 121 aneurysms from 511 (24%) were recanalized on follow up angiography, 52 required retreatment (7.1%). At 6 months follow up, 580 patients (82%) were independent, while 130 patients (18%) were disabled or dead. CONCLUSION: Detachable coil embolisation of intracranial aneurysms is a very feasible treatment method associated with a small risk of permanent morbidity-mortality. Risk of further bleeding is small, but related with devastating outcome. Approximately 25% of aneurysms will recanalize and 7% will require retreatment. Despite these shortcomings, vast majority of patients will achieve independent recovery.

Retreatment of previously embolized cerebral aneurysms: the risk of further coil embolization does not negate the advantage of the initial embolization.

BACKGROUND AND PURPOSE: A significant minority of aneurysms treated by endovascular means undergo additional subsequent therapy to treat aneurysm recurrence. Our study was undertaken to determine the risk of additional coil embolization of aneurysms recurring following endovascular therapy. MATERIALS AND METHODS: Patients were identified during a 10-year period from prospectively collated data bases at 2 different neuroscience institutions. Patient outcome was obtained from the data bases or the patient's neurosurgical records. Occlusion grade was assessed at the time of treatment and at follow-up angiography as complete, near-complete, or incomplete. RESULTS: Of a total of 1834 aneurysms in 1631 patients, 100 aneurysms in 99 patients treated between January 1996 and December 2005 required additional coiling because of an enlarging remnant and subtotal occlusion. This comprised 6% of the patients treated and 8% of the total followed. Thromboembolic events complicated 3 retreatment procedures, but all 3 patients remain independent. Ninety-five patients were followed for 8-103 months (mean, 42.3 months) by conventional or MR angiography. CONCLUSION: Coil embolization of aneurysm recurrences has a low complication rate and leads to satisfactory occlusion in most cases. The risk from additional coil embolization does not negate the advantage of the initial embolization.

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.

ICONE: An International Consortium of Neuro Endovascular Centres.

SUMMARY: The proliferation of new endovascular devices and therapeutic strategies calls for a prudentand rational evaluation of their clinical benefit. This evaluation must be done in an effective manner and in collaboration with industry. Such research initiative requires organisation a land methodological support to survive and thrive in a competitive environment. We propose the formation of an international consortium, an academic alliance committed to the pursuit of effective neurovascular therapies. Such a consortium would be dedicated to the designand execution of basic science, device developmentand clinical trials. The Consortium is owned and operated by its members. Members are international leaders in neurointerventional research and clinical practice. The Consortium brings competency, knowledge, and expertise to industry as well as to its membership across aspectrum of research initiatives such as: expedited review of clinical trials, protocol development, surveys and systematic reviews; laboratory expertise and support for research design and grant applications to public agencies. Once objectives and protocols are approved, the Consortium provides a stable network of centers capable of timely realization of clinical trials or pre clinical investigations in an optimal environment. The Consortium is a non-profit organization. The potential revenue generated from clientsponsored financial agreements will be redirected to the academic and research objectives of the organization. The Consortium wishes to work inconcert with industry, to support emerging trends in neurovascular therapeutic development. The Consortium is a realistic endeavour optimally structured to promote excellence through scientific appraisal of our treatments, and to accelerate technical progress while maximizing patients' safety and welfare.

Unruptured Intracranial Aneurysms. A Critical Review of the International Study of Unruptured Intracranial Aneurysms (ISUIA) and of Appropriate Methods to Address the Clinical Problem.

SUMMARY: The preventive treatment of unruptured aneurysms has been performed for decades despite the lack of evidence of a clinical benefit. Reports of observational studies such as the International Study of Unruptured Intracranial Aneurysms (ISUIA) suggest that preventive treatments are rarely justified. Are these reports compelling enough to guide clinical practice? The ISUIA methods and data are reviewed and analysed in a more conventional manner. The design of the appropriate clinical research program is approached by steps, reviewing potential problems, from the formulation of the precise research question to the interpretation of subgroup analyses, including sample size, representativity, duration of observation period, blinding, definition of outcome events, analysis of cross-overs, losses to follow-up, and data reporting. Unruptured intracranial aneurysms observed in ISUIA ruptured at a minimal annual rate of 0.8% (0.5-1%), despite multiple methodological difficulties biased in favour of a benign natural history. Available registries do not have the power or the design capable of providing normative guidelines for clinical decisions. The appropriate method to solve the clinical dilemma is a multicentric trial comparing the incidence of a hard clinical outcome events in approximately 2000 patients randomly allocated to a treatment group and a deferred treatment group, all followed for ten years or more. Observational studies have failed to provide reliable evidence in favour or against the preventive treatment of unruptured aneurysms. A randomized trial is in order to clarify what is the role of prevention in this common clinical problem.

Findings of the International Subarachnoid Aneurysm Trial and the National Study of Subarachnoid Haemorrhage in context.

Concern has been expressed about the applicability of the findings of the International Subarachnoid Aneurysm Trial (ISAT) with respect to the relative effects on outcome of coiling and clipping. It has been suggested that the findings of the National Study of Subarachnoid Haemorrhage may have greater relevance for neurosurgical practice. The objective of this paper was to interpret the findings of these two studies in the context of differences in their study populations, design, execution and analysis. Because of differences in design and analysis, the findings of the two studies are not directly comparable. The ISAT analysed all randomized patients by intention-to-treat, including some who did not undergo a repair, and obtained the primary outcome for 99% of participants. The National Study only analysed participants who underwent clipping or coiling, according to the method of repair, and obtained the primary outcome for 91% of participants. Time to repair was also considered differently in the two studies. The comparison between coiling and clipping was susceptible to confounding in the National Study, but not in the ISAT. The two study populations differed to some extent, but inspection of these differences does not support the view that coiling was applied inappropriately in the National Study. Therefore, there are many reasons why the two studies estimated different sizes of effect. The possibility that there were real, systematic differences in practice between the ISAT and the National Study cannot be ruled out, but such explanations must be seen in the context of other explanations relating to chance, differences in design or analysis, or confounding.

Change in incidence and aetiology of intracerebral haemorrhage in Oxfordshire, UK, between 1981 and 2006: a population-based study.

BACKGROUND: UK stroke mortality data suggest that the incidence of haemorrhagic stroke has fallen in the past 20 years, but these data do not include deaths of individuals aged 75 years or over. Trends in the older population might differ, since cause varies with age. Our aim was to investigate changes in the population-based incidence of intracerebral haemorrhage according to age and likely aetiology. METHODS: We used data from the Oxford Community Stroke Project (OCSP; 1981-86) and the Oxford Vascular Study (OXVASC; 2002-06) to investigate changes in the incidence of intracerebral haemorrhage with time, above and below age 75 years, together with associated risk factors and premorbid medications. Incidences were standardised to the 2001 census population of England and Wales. FINDINGS: In the population aged under 75 years the incidence of intracerebral haemorrhage decreased substantially (rate ratio 0.53, 95% CI 0.29-0.95; p=0.03), but the number of cases of intracerebral haemorrhage at all ages were similar in OXVASC and OCSP (52 vs 55 cases) as the proportion of cases occurring at 75 years and over tended to increase (2.0, 0.8-4.6; p=0.09). The incidence of intracerebral haemorrhage associated with premorbid hypertension (blood pressure >or=160/100 mm Hg) fell overall (0.37, 0.20-0.69; p=0.002), but the incidence of intracerebral haemorrhage associated with antithrombotic use was increased (7.4, 1.7-32; p=0.007). Above age 75 years the proportion of cases who were non-hypertensive with lobar bleeds and presumed to have had mainly amyloid-related haemorrhages, also increased (4.0, 1.1-17; p=0.003). INTERPRETATION: There has been a substantial fall in hypertension-associated intracerebral haemorrhage over the past 25 years, but not in the overall number of cases of intracerebral haemorrhage in older age-groups, in part due to a rise in intracerebral haemorrhage associated with antithrombotic use. These trends, along with the expected increase in prevalence of amyloid angiopathy with the ageing population, suggest that, in contrast to projections based on mortality data below age 75 years, absolute number of cases of intracerebral haemorrhage might increase in future.

Trial on endovascular treatment of unruptured aneurysms (TEAM): study monitoring and rationale for trial interruption or continuation.

Preventive treatment of unruptured intracranial aneurysms is often performed but has never been proved beneficial as compared to conservative management. In a context of uncertainty, the 'best treatment' that can be offered to each individual is a chance to be treated and thus to be protected from rupture of the aneurysm, and an equal chance not to be treated, and hence to be exempted from possible immediate complications, using randomization. Such action is optimal unless or until an independent committee with privileged access to data judges that, given the comparative outcome of the 2 groups, preventive treatment or conservative management, is generally warranted. Potential reasons to interrupt such a study are reviewed, including insufficient recruitment, poor compliance, excessive cross-overs, unacceptable iatrogenia, and treatments being convincingly different or equivalent. We conclude that insufficient recruitment is the sole realistic event that could lead to premature interruption. This review may provide a deeper understanding of the principles justifying the necessity of the study.

Rapid review in cervical cytology: a retrospective review of cases detected on rapid review within a DGH cytology department and subsequent outcome.

We retrospectively reviewed smears detected by rapid review within a district general hospital (DGH) laboratory over a period of 33 months and the subsequent histological or cytological outcome. Sixty-three cases had adequate follow-up data: 32 subsequently had two negative smears and 31 had a histological abnormality on subsequent biopsy. Twenty were high-grade lesions (CIN2, CIN3 or a glandular lesion) and eight of these were preceded by a low-grade smear abnormality. We reviewed and compared the pattern and distribution of smear abnormalities in these 63 cases. Abnormalities were often present within few cells (76%, n = 48 with 50 abnormal cells or less) or in micro-biopsies (27%, n = 17). There was no statistical difference in the pattern and distribution of smear abnormality between the rapid review-detected smears with a biopsy-proven abnormality and those with negative follow-up smears. Overall, the positive predictive value for high-grade CIN detected by rapid review (75%) was within NHSCSP achievable standards targets. This review of rapid review-detected abnormalities and the biopsy and cytological follow-up reiterates the importance of the method in cervical screening.

Embolisation of spinal dural arteriovenous fistulae with Onyx.

Surgery is currently the standard treatment for spinal dural arteriovenous fistulae (DAVF). Endovascular embolisation of these lesions using N-butyl cyanoacrylate (NBCA) has a high success rate. Onyx is a new liquid embolic agent whose viscosity makes it suitable for treatment of spinal DAVF where penetration into the proximal radicular vein is required. It is delivered with greater control than NBCA without the necessity for rapid withdrawal of the catheter and may therefore overcome some of the drawbacks of NBCA. We report two patients who underwent Onyx embolisation of spinal DAVF; to our knowledge this is the first such report.