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Irene Meissner, James Torner, John Huston III, Michele L. Rajput, David O. Wiebers, Lyell K. Jones Jr., Robert D. Brown Jr. and the International Study of Unruptured Intracranial Aneurysms Investigators

Object

Investigators conducting the International Study of Unruptured Intracranial Aneurysms, sponsored by the National Institutes of Health, sought to evaluate predictors of future hemorrhage in patients who had unruptured mirror aneurysms. These paired aneurysms in bilateral arterial positions mirror each other; their natural history is unknown.

Methods

Centers in the US, Canada, and Europe enrolled patients for prospective assessment of unruptured intracranial aneurysms. Central radiological review confirmed the presence or absence of mirror aneurysms in patients without a history of prior subarachnoid hemorrhage (SAH) (Group 1). Outcome at 1 and 5 years and aneurysm characteristics are compared.

Results

Of 3120 patients with aneurysms treated in 61 centers, 376 (12%) had mirror aneurysms, which are more common in women than men (82% [n = 308] vs 73% [n = 1992], respectively; p <0.001) and in patients with a family history of aneurysm or SAH (p <0.001).

Compared with patients with nonmirror saccular aneurysms, a greater percentage of patients with mirror aneurysms had larger (>10 mm) aneurysms (mean maximum diameter 11.7 vs 10.4 mm, respectively; p <0.001). The most common distribution for mirror aneurysms was the middle cerebral artery (34% [126 patients]) followed by noncavernous internal carotid artery (32% [121]), posterior communicating artery (16% [60]), cavernous internal carotid artery (13% [48]), anterior cerebral artery/anterior communicating artery (3% [13]), and vertebrobasilar circulation (2% [8]). When these patients were compared with patients without mirror aneurysms, no statistically significant differences were found in age (mean age 54 years in both groups), blood pressure, smoking history, or cardiac disease. Aneurysm rupture rates were similar (3.0% for patients with mirror aneurysms vs 2.8% for those without).

Conclusions

Overall, patients with mirror aneurysms were more likely to be women, to report a family history of aneurysmal SAH, and to have larger aneurysms. The presence of a mirror aneurysm was not an independent predictor of future SAHs.

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Kelly D. Flemming, David O. Wiebers, Robert D. Brown Jr., Michael J. Link, Hirofumi Nakatomi, John Huston III, Robyn McClelland and Teresa J. H. Christianson

Object. Nonsaccular intracranial aneurysms (NIAs) are characterized by dilation, elongation, and tortuosity of intracranial arteries. Dilemmas in management exist due to the limited regarding the natural history of this disease entity. The objective of this study was to determine the prospective risk of subarachnoid hemorrhage (SAH) in patients with vertebrobasilar NIAs.

Methods. All patients with vertebrobasilar fusiform or dolichoectatic aneurysms that had been radiographically demonstrated between 1989 and 2001 were identified. These patients' medical records were retrospectively reviewed. A prospective follow-up survey was sent and death certificates were requested. Based on results of neuroimaging studies, the maximal diameter of the involved artery, presence of SAH, and measurements of arterial tortuosity were recorded. Nonsaccular intracranial aneurysms were classified according to their radiographic appearance: fusiform, dolichoectatic, and transitional. Dissecting aneurysms were excluded. The aneurysm rupture rate was calculated based on person-years of follow up. Predictive factors for rupture were evaluated using univariate analysis (p < 0.05). One hundred fifty-nine patients, 74% of whom were men, were identified. The mean age at diagnosis was 64 years (range 20–87 years). Five patients (3%) initially presented with hemorrhage; four of these patients died during follow up. The mean duration of follow up was 4.4 years (692 person-years). Nine patients (6%) experienced hemorrhage after presentation; six hemorrhages were definitely related to the NIA. The prospective annual rupture rate was 0.9% (six patients/692 person-years) overall and 2.3% in those with transitional or fusiform aneurysm subtypes. Evidence of aneurysm enlargement or transitional type of NIA was a significant predictor of lesion rupture. Six patients died within 1 week of experiencing lesion rupture.

Conclusions. Risk of hemorrhage in patients harboring vertebrobasilar NIAs is more common in those with evidence of aneurysm enlargement or a transitional type of aneurysm and carries a significant risk of death.

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Editorial

Unruptured aneurysms

David O. Wiebers, David G. Piepgras, Robert D. Brown Jr., Irene Meissner, James Torner, Neal F. Kassell, Jack P. Whisnant, John Huston III and Douglas A. Nichols

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Robert D. Ecker, Robert D. Brown Jr, Douglas A. Nichols, Robyn L. McClelland, Megan S. Reinalda, David G. Piepgras, Harry J. Cloft and David F. Kallmes

Object. Definitive data characterizing the safety and efficacy of carotid angioplasty with stent placement (CAS) for symptomatic, occlusive carotid artery (CA) disease require further refinements and standardization of techniques as well as large prospective studies on a par with the North American Symptomatic Carotid Endarterectomy Trial (NASCET). Despite the absence of such data, many surgeons have performed angioplasty and stent placement in patients with clinical or anatomical features known to add significant perioperative risk and capable of disqualifying the patients from participation in NASCET. There exists no cost analysis comparing high-risk endarterectomy with percutaneous angioplasty and stent insertion.

Methods. Forty-five patients (29 men and 16 women) with high-risk, symptomatic CA stenosis have been treated with CAS at the authors' institution since 1996. Indications for this procedure included symptomatic recurrent stenosis following CA endarterectomy (CEA), active coronary disease, high CA bifurcation, and severe medical comorbidities. A long-standing CEA computer database was screened for control patients with similar risk factors; 391 patients (276 men and 115 women) were identified. Actual cost data, duration of hospital stay, and relevant clinical data from the time of treatment until hospital discharge were collected in each patient. The median total cost of CAS was $10,628, whereas that for CEA was $10,148 (p = 0.495).

Conclusions. In patients with high-risk, NASCET-ineligible CA stenosis there was no overall statistically significant cost difference between CEA and CAS. Given that there may not be a cost advantage for either procedure, procedural risk, efficacy, and durability should be key factors in determining the optimal treatment strategy.

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Lisa Anne Cannon-Albright

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Robert D. Brown JR., John Huston III, Richard Hornung, DR.P.H., Tatiana Foroud, David F. Kallmes, Dawn Kleindorfer, Irene Meissner, Daniel Woo, Laura Sauerbeck, Joseph Broderick and for the Familial Intracranial Aneurysm (FIA) Investigators

Object

Approximately 20% of patients with an intracranial saccular aneurysm report a family history of intracranial aneurysm (IA) or subarachnoid hemorrhage. A better understanding of predictors of aneurysm detection in familial IA may allow more targeted aneurysm screening strategies.

Methods

The Familial Intracranial Aneurysm (FIA) study is a multicenter study, in which the primary objective is to define the susceptibility genes related to the formation of IA. First-degree relatives (FDRs) of those affected with IA are offered screening with magnetic resonance (MR) angiography if they were previously unaffected, are ≥ 30 years of age, and have a history of smoking and/or hypertension. Independent predictors of aneurysm detection on MR angiography were determined using the generalized estimating equation version of logistic regression.

Results

Among the first 303 patients screened with MR angiography, 58 (19.1%) had at least 1 IA, including 24% of women and 11.7% of men. Ten (17.2%) of 58 affected patients had multiple aneurysms. Independent predictors of aneurysm detection included female sex (odds ratio [OR] 2.46, p = 0.001), pack-years of cigarette smoking (OR 3.24 for 20 pack-years of cigarette smoking compared with never having smoked, p < 0.001), and duration of hypertension (OR 1.26 comparing those with 10 years of hypertension to those with no hypertension, p = 0.006).

Conclusions

In the FIA study, among the affected patients' FDRs who are > 30 years of age, those who are women or who have a history of smoking or hypertension are at increased risk of suffering an IA and should be strongly considered for screening.

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Yasunori Nagahama, Lauren Allan, Daichi Nakagawa, Mario Zanaty, Robert M. Starke, Nohra Chalouhi, Pascal Jabbour, Robert D. Brown Jr., Colin P. Derdeyn, Enrique C. Leira, Joseph Broderick, Marc Chimowitz, James C. Torner and David Hasan

OBJECTIVE

Clinical vasospasm and delayed cerebral ischemia (DCI) are devastating complications of aneurysmal subarachnoid hemorrhage (aSAH). Several theories involving platelet activation have been postulated as potential explanations of the development of clinical vasospasm and DCI. However, the effects of dual antiplatelet therapy (DAPT; aspirin and clopidogrel) on clinical vasospasm and DCI have not been previously investigated. The objective of this study was to evaluate the effects of DAPT on clinical vasospasm and DCI in aSAH patients.

METHODS

Analysis of patients treated for aSAH during the period from July 2009 to April 2014 was performed in a single-institution retrospective study. Patients were divided into 2 groups: patients who underwent stent-assisted coiling or placement of flow diverters requiring DAPT (DAPT group) and patients who underwent coiling only without DAPT (control group). The frequency of symptomatic clinical vasospasm and DCI and of hemorrhagic complications was compared between the 2 groups, utilizing univariate and multivariate logistic regression.

RESULTS

Of 312 aSAH patients considered for this study, 161 met the criteria for inclusion and were included in the analysis (85 patients in the DAPT group and 76 patients in the control group). The risks of clinical vasospasm (OR 0.244, CI 95% 0.097–0.615, p = 0.003) and DCI (OR 0.056, CI 95% 0.01–0.318, p = 0.001) were significantly lower in patients receiving DAPT. The rates of hemorrhagic complications associated with placement of external ventricular drains and ventriculoperitoneal shunts were similar in both groups (4% vs 2%, p = 0.9).

CONCLUSIONS

The use of DAPT was associated with a lower risk of clinical vasospasm and DCI in patients treated for aSAH, without an increased risk of hemorrhagic complications.

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Jason Mackey, Robert D. Brown Jr., Charles J. Moomaw, Laura Sauerbeck, Richard Hornung, Dheeraj Gandhi, Daniel Woo, Dawn Kleindorfer, Matthew L. Flaherty, Irene Meissner, Craig Anderson, E. Sander Connolly, Guy Rouleau, David F. Kallmes, James Torner, John Huston III and Joseph P. Broderick

Object

Familial predisposition is a recognized nonmodifiable risk factor for the formation and rupture of intracranial aneurysms (IAs). However, data regarding the characteristics of familial IAs are limited. The authors sought to describe familial IAs more fully, and to compare their characteristics with a large cohort of nonfamilial IAs.

Methods

The Familial Intracranial Aneurysm (FIA) study is a multicenter international study with the goal of identifying genetic and other risk factors for formation and rupture of IAs in a highly enriched population. The authors compared the FIA study cohort with the International Study of Unruptured Intracranial Aneurysms (ISUIA) cohort with regard to patient demographic data, IA location, and IA multiplicity. To improve comparability, all patients in the ISUIA who had a family history of IAs or subarachnoid hemorrhage were excluded, as well as all patients in both cohorts who had a ruptured IA prior to study entry.

Results

Of 983 patients enrolled in the FIA study with definite or probable IAs, 511 met the inclusion criteria for this analysis. Of the 4059 patients in the ISUIA study, 983 had a previous IA rupture and 657 of the remainder had a positive family history, leaving 2419 individuals in the analysis. Multiplicity was more common in the FIA patients (35.6% vs 27.9%, p < 0.001). The FIA patients had a higher proportion of IAs located in the middle cerebral artery (28.6% vs 24.9%), whereas ISUIA patients had a higher proportion of posterior communicating artery IAs (13.7% vs 8.2%, p = 0.016).

Conclusions

Heritable structural vulnerability may account for differences in IA multiplicity and location. Important investigations into the underlying genetic mechanisms of IA formation are ongoing.

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Daichi Nakagawa, Yasunori Nagahama, Bruno A. Policeni, Madhavan L. Raghavan, Seth I. Dillard, Anna L. Schumacher, Srivats Sarathy, Brian J. Dlouhy, Saul Wilson, Lauren Allan, Henry H. Woo, John Huston III, Harry J. Cloft, Max Wintermark, James C. Torner, Robert D. Brown Jr. and David M. Hasan

OBJECTIVE

Aneurysm growth is considered predictive of future rupture of intracranial aneurysms. However, how accurately neuroradiologists can reliably detect incremental aneurysm growth using clinical MRI is still unknown. The purpose of this study was to assess the agreement rate of detecting aneurysm enlargement employing generally used MRI modalities.

METHODS

Three silicone flow phantom models, each with 8 aneurysms of various sizes at different sites, were used in this study. The aneurysm models were identical except for an incremental increase in the sizes of the 8 aneurysms, which ranged from 0.4 mm to 2 mm. The phantoms were imaged on 1.5-T and 3-T MRI units with both time-of-flight (TOF) and contrast-enhanced MR angiography. Three independent expert neuroradiologists measured the aneurysms in a blinded manner using different measurement approaches. The individual and agreement detection rates of aneurysm enlargement among the 3 experts were calculated.

RESULTS

The mean detection rate of any increase in any aneurysmal dimension was 95.7%. The detection rates of the 3 observers (observers A, B, and C) were 98.0%, 96.6%, and 92.7%, respectively (p = 0.22). The detection rates of each MRI modality were 91.3% using 1.5-T TOF, 97.2% using 1.5-T with Gd, 95.8% using 3.0-T TOF, and 97.2% using 3.0-T with Gd (p = 0.31). On the other hand, the mean detection rate for aneurysm enlargement was 54.8%. Specifically, the detection rates of observers A, B, and C were 49.0%, 46.1%, and 66.7%, respectively (p = 0.009). As the incremental enlargement value increased, the detection rate for aneurysm enlargement increased. The use of 1.5-T Gd improved the detection rate for small incremental enlargement (e.g., 0.4–1 mm) of the aneurysm (p = 0.04). The location of the aneurysm also affected the detection rate for aneurysm enlargement (p < 0.0001).

CONCLUSIONS

The detection rate and interobserver agreement were very high for aneurysm enlargement of 0.4–2 mm. The detection rate for at least 1 increase in any aneurysm dimension did not depend on the choice of MRI modality or measurement protocol. Use of Gd improved the accuracy of measurement. Aneurysm location may influence the accuracy of detecting enlargement.