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oncurrent Intracranial and Thoracic Aortic Aneurysms

udy J. Rahme, H. Hunt Batjer, William H. Pearce, Eric J. Russell, Bernard R. Bendok

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espite the high prevalence of intracranial aneurysms (ICAs) and thessociated morbidity of rupture, no criteria have yet been developed forcreening the general population. Improvements in magnetic reso-ance angiography sensitivity, a reduction in its cost, and greater in-ight into risk factors could pave the way for a rational screening ap-roach. Aortic and intracranial aneurysms have been historicallyegarded as very different diseases, but recent biological studies haveuggested some commonalities. Recently, a link between the two enti-ies has been suggested but it has not been well established. To betternderstand this potential association, Kuzmik et al. from the Yale Uni-ersity School of Medicine (Am J Cardiol 2010 105:417-420.) analyzed560 patients who underwent thoracic aortic aneurysm (TAA) repairnd found that 212 of them also had an ICA. Fifty-two patients wereound retrospectively, and 160 were found prospectively.

The patients were categorized based on the location of their TAAnto those with ascending TAA and those with descending TAA. Theuthors found a 9% prevalence of ICA in their TAA group comparedo the 1% prevalence in the general population (in the prospectiveubgroup, the prevalence was 6.3%). ICA prevalence in the descend-ng TAA subgroup was significantly higher than in the ascendingAA subgroup, a difference that persisted when only the prospectiveatients were taken into account but without reaching statisticalignificance. The authors then analyzed the relation of known riskactors and epidemiological parameters to the ICA–TAA associationFigure 1). Hypertension was noted to be significantly associatedith an increased risk of ICA presence in TAA patients, a trend also

een in the prospective group but without statistical significance.moking was found to be a significant factor exclusively in therospective group (P � 0.05). All other studied factors (age, gender,nd race) were not found to be statistically significant.

In the not too distant future, genetic, familial, and environmental riskactors will likely be used to compute one’s risk for ICA disease. This

ay form the basis for rational screening, prevention and preemptivereatment. This study draws our attention to a potential relationship

etween two diseases with significant risk to aging populations around D

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uch studies assess risk factors associated with ruptured and/or

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ORLD NEUROSURGERY 73 [4]: 231-238, APRIL 2010

he world. These two diseases have been studied in isolation for theost part. A closer look at areas of commonality and larger prospective

pidemiological studies are warranted. Given the heterogeneity of an-urysm diseasees in varying ethnic groups and geographic regions, annternational approach to such studies is preferable.

878-8750/$ - see front matter © 2010 Published by Elsevier Inc.

Figure 1. Subgroup analysis of intracranial aneurysm incidence in thoracicaortic aneurysm patients in relation to (A) specific risk factor and (B)epidemiologic parameters. Error bars represent 95% confidence interval.ICA: Intracranial Aneurysms; TAA: Thoracic Aortic Aneurysm; HTN:Hypertension. Reprinted from The American Journal of Cardiology 105;Kuzmik et al., Concurrent Intracranial and Thoracic Aortic Aneurysms,417-420, Copyright 2010, with permission from Elsevier.

OI: 10.1016/j.wneu.2010.02.048

he Development of a Calculator to Predict the Risk of Rupture ofnruptured Intracranial Aneurysms—@neuRisk

he information from studies on the risk of rupture of unrupturedntracranial aneurysms (UIA) is variable and inconclusive. Although

nruptured intracranial aneurysms (IAs) and aim to make predic-ions on the annual risk of rupture of UIAs, specific risk factors are

enerally analyzed in isolation and only very infrequently are consid-

www.WORLDNEUROSURGERY.org 231

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red alongside other variables. In the absence of consideration ofhe many diverse and disparate risk factors, current risk prediction

odels are somewhat approximate and inaccurate. At the presentime, the seminal 1998 NEJM (2) and 2003 Lancet (7) ISUIA papersre considered to provide the neuroscience clinician with the bestnformation to determine the risk of rupture of UIAs with correla-ions that are primarily based on the size of the aneurysm.

The availability of a tool (a calculator) able to integrate and analyzenown risk factors would enable the prediction of the risk of ruptureor an individual aneurysm in a particular patient with greater accu-acy and would therefore have profound implications in the treat-

ent of these unfortunate patients.The @neurIST initiative was developed to achieve just such a feat (4).

n information technology infrastructure has been developed withinneurIST to integrate heterogenous data (risk factors) associated with

erebral aneurysms and subarachnoid hemorrhage (SAH). The ulti-ate aim is to provide Neuroscience Clinicians with a user-friendly

nterface to give a patient-specific prediction of the risk of rupture. Thisntegrated Project has received funding of 17 million euros from theuropean Commission (Framework 6) over 4 years. The @neurISTonsortium involves a multidisciplinary team, including neurosur-eons, interventional neuroradiologists, epidemiologists, engineers,iologists, medical physicists, and computer scientists from 32 Euro-ean institutions (both public and private) in 12 countries and includes

nternational collaboration with groups in George Mason University,niversity of Auckland, Tohoku University, and Yale. Although this

rticle is focused on @neuRisk—a program that is directed toward thentegration of all available data to obtain a personalized risk assessmentn an individual aneurysm, the project has a number of other aspects,

ncluding @neuLink, identification of genes associated with the diseasend integration with epidemiological and clinical data; @neuFuse, fu-ion of diagnostic and modeled data into a coherent representation ofhe patient’s state; and @neuEndo, assist the development of implant-ble devices (flow diversion stents) from simulation of morphological,emodynamic, and biological factors.

A detailed, comprehensive systematic evaluation of published re-iews of risk factors has been performed, in part for @neurIST (1),sing PubMed and EMBASE. Twenty-four risk factors were studiednd it was concluded that nonwhite racial origin, older age, femaleender, family history, autosomal polycystic kidney disease, hyper-

ension, smoking, low body mass index, alcohol consumption ofore than 150 g per week, larger aneurysms, posterior circulation

neurysms, previous SAH, and previous symptoms were associatedith a higher risk of SAH. There was a lower risk of SAH associatedith high cholesterol, diabetes, and the use of hormone replace-ent therapy. The contribution of other factors, namely, aneurysmorphology, physiology, and hemodynamics, were not considered.To address these in @neurIST, the University of Sheffield and the

heffield Teaching Hospitals National Health Service Trust are playingmajor role in the development of image-processing and computa-

ional tools to provide novel, nonobservational, clinically useful mea-ures to characterize the disease using computational fluid dynamicsCFD). This is an established methodology developed for the aerospacend motor industries. CFD has enabled specific questions to be ad-ressed in the analysis of UIAs (Figure 1). For example, it has beenhown that, under certain proximal flow conditions, the hemodynamicharacterization of IAs is insensitive to the inlet velocity profile (3). The

emodynamic variables associated with the etiopathogenesis of IAs c

32 www.SCIENCEDIRECT.com

nclude wall shear stress (WSS), oscillatory shear index (OSI), and bloodressure. High WSS is associated with development and low WSS withrowth and rupture of IAs, whereas high or low OSI correlates withevelopment and low OSIs with growth and rupture (6). This paper alsossessed clinician acceptance and received positive feedback. The cor-elations identified require further validation against the available clin-cal information.

A paper presented to the WFNS in Boston on the effects of viscosityn the natural history of IAs received the Young Neurosurgeon’s Award7). Other work has studied the effects of smoking and hypertension on

SS and OSI. An analysis was performed on the hemodynamics ofntracranial aneurysms of the anterior and posterior circulation and thessociation with rupture (5). The @neurIST software was used to recon-truct the neurovasculature of the region of interest and compute areasf the aneurysmal endothelium exposed to infraphysiological (�0.4 Pa)nd high wall shear stress (WSS) (�1.5 Pa). Other risk factors com-only associated with IAs (age, gender, smoking, hypertension, etc.)ere covariates in the statistical analysis. Analysis of covariance (AN-OVA) was used to compare data of the anterior and posterior circula-

ion. The results correlated with established studies on the risk of rup-ure (2). There were significant differences between the levels of WSS inhe anterior and posterior circulations, which concurred with publishedtudies (2, 8). The areas of infraphysiological WSS might be correlatedith endothelial disruption, whereas those areas associated with sup-

aphysiological WSS may be associated with IA initiation.The final review of the @neurIST project, and of its tools, took

lace in March 2010 in Barcelona, Spain. Strategies for maintenancef its databases are under active discussion with a professional soci-ty, and individual partners have their own plans for making avail-ble components of the tool-chains (personal communications). Itill then be the work of Neuroscience Clinicians to test these and

Figure 1. Computational fluid dynamics predictions of an anterior cerebralartery saccular aneurysm. (A) contours of wall shear stress. (B) contoursof oscillatory shear index. (C) flow streamlines. (D) jet impingement andpressure elevation on the aneurysmal wall.

ompare their results to established studies. It is anticipated that

73 [4]: 231-238, APRIL 2010 WORLD NEUROSURGERY

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hese tools will contribute to the determination of the risk of ruptureor an individual UIA, providing more accurate prognoses with as-ociated health and economic benefits.

CKNOWLEDGMENTS

he author wishes to acknowledge the contribution of theneurIST team at Sheffield, PV Lawford, A Marzo, P Singh, SC

oley, DR Hose. @neurIST Project: IST-2004-027703 funded by (

. Patel U, Marzo A, Waterworth A, Hose DR, Frangi A,Lawford P, McCormack K, Coley S: Development of a

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7. Singh PK, Marzo A, Tahir H,Lawford P, Patel U, Hose R.

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erformed in 2007 in noncancer patients with at least 5 years of life left.

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ORLD NEUROSURGERY 73 [4]: 231-238, APRIL 2010

he European Commission. Sixth Framework Programme, Prior-ty 2, Information Society Technologies.

Clinical centres: The University Hospital of Geneva, The Royalallamshire Hospital (Sheffield Teaching Hospital NHS Founda-

ion Trust), Erasmus Universitair Medisch Centrum Rotterdam, Thehancellor Masters and Scholars of the University of Oxford, Neu-

oangiografia Terapèutica S.L. (Hospital General de Catalunya),ospital Clínic i Provincial de Barcelona, Pecsi Tudomanyegyetem

The University Medical Center of Pecs)

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EFERENCES

. Clarke M: Systematic review of reviews of risk factorsfor intracranial aneurysms. Neuroradiology 50: 653-664, 2008.

. International Study of Unruptured Intracranial Aneu-rysms Investigators. Unruptured intracranial aneu-rysms—risk of rupture and risks of surgical interven-tion. N Engl J Med 339:1725-1733, 1998.

. Marzo A, Singh PK, Reymond P, Stergiopulos N, Pa-tel U, Hose R: Influence of inlet boundary conditionson the local haemodynamics of intracranial aneu-rysms. Comput Methods Biomech Biomed Engin12(4):431-444, 2009.

computational model to determine the risk ofaneurysm rupture. European Congress of Neurosur-gery SECC, September 2007, Glasgow, UK.

. Pitt A, Marzo A, Singh P, Aguilar M, Larrabide I,Frangi A, Hose DR, Lawford P, Patel, UJ: Haemody-namics in intracranial aneurysms of the anterior andposterior circulation and its association with rupture.Abstract submitted to the Society of British Neuro-logical Surgeons, 2010.

. Singh P, Marzo A, Coley SC, Berti G, Bijlenga P, Law-ford PV, Villa-Uriol MC, Rufenacht DA, McCormackKM, Frangi A, Patel UJ, Hose R: The role of computa-tional fluid dynamics in the management of unrup-tured intracranial aneurysms: a clinicians’ view.Comput Intel Neurosci760364, 2009 (Epub 2009August 19).

Weeratunge T, Coley SC,Analysis of different he-

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modynamic factors during initiation and rupture ofintracranial aneurysms and influence of variousdrugs on their natural history. Proceedings of XIVWorld Congress of Neurological Surgery August-September 2009, Boston, USA.

. Wiebers DO, Whisnant JP, Huston J 3rd, Meissner I,Brown RD Jr, Piepgras DG, Forbes GS, Thielen K,Nichols D, O’Fallon WM, Peacock J, Jaeger L, KassellNF, Kongable-Beckman GL, Torner JC; InternationalStudy of Unruptured Intracranial Aneurysms Investi-gators: Unruptured intracranial aneurysms: naturalhistory, clinical outcome, and risks of surgical andendovascular treatment. Lancet 362:103-110, 2003.

878-8750/$ - see front matter © 2010 Elsevier Inc. All rights

eserved.OI: 10.1016/j.wneu.2010.02.052

he Sunset of the CT Scan?

hen the first computed tomographic (CT) scan of the head wasbtained, it ushered in a miraculous new age for neurosurgery.eurosurgeons were granted an almost magical ability to peer into

he human brain that had been sought for ages. Within a short time,he head CT scan became the most indispensable diagnostic tool ofhe profession. As the technology evolved, it became increasinglyapid, convenient, and relatively inexpensive, and hence proliferatedhroughout the world.

Alas, like CFC-based propellants and Scotchguard, the CT scan has aajor, and possibly fatal, flaw. Despite its great utility, the CT scan’s

ark underbelly is the ionizing radiation that is required to create themages we see. Two new studies published as companion pieces in therchives of Internal Medicine (169[22]:2071-2077, 2009, and Arch Interned, 169[22]:2078-2086, 2009) highlight these concerns. The first, by

errington de González et al., establishes risk models using knownata on radiation doses and cancer rates. The authors conclude that9,000 future cancers will be attributable to the 57 million CT scans

he risk of cancer is inversely related to the age of the patient at the timef exposure. In this study, the estimated risk of cancer from a head CTerformed at age 3 is between 8 and 9 per 10,000 scans. At age 30, theisk is 2 to 3 per 10,000 scans.

Arguably, a 30-year-old patient admitted to the hospital with a headnjury and loss of consciousness has greater than a 2 to 3 per 10,000hance of benefiting from the information that a head CT would pro-ide. But is every scan we performed strictly necessary? What is notddressed, and is worrisomely unknown, is what the risks are for theignificant number of neurosurgical patients with hydrocephalus and ahunt who have received 5, 10, 50, or 100 or more head CT scans. Theres little data on the cumulative risk of multiple scans to guide us whenalculating risk and benefit. For many patients with present risks fromonditions where a CT scan would be of benefit, the immediate needrumps the longer-term concerns of cancer. But as scans become moreommon, the risk will grow to the point where it cannot be ignored. Theuthors note that three times as many CT scans of all types were per-

93. They estimate that cancers attributable to

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