CLINICAL ARTICLEJ Neurosurg 128:982–991, 2018

ABBREVIATIONS DSA = digital subtraction angiography; DWI = diffusion-weighted imaging; FLAIR = fluid-attenuated inversion recovery; MMSE = Mini–Mental State Examination; mRS = modified Rankin Scale; OKM = O’Kelly-Marotta; PRU = P2Y12 reaction unit; r = correlation coefficient; R2 = coefficient of determination.SUBMITTED April 25, 2016. ACCEPTED November 21, 2016.INCLUDE WHEN CITING Published online June 9, 2017; DOI: 10.3171/2016.11.JNS161020.

Evaluation of ischemic lesion prevalence after endovascular treatment of intracranial aneurysms, as documented by 3-T diffusion-weighted imaging: a 2-year, single-center cohort studyChristina Iosif,1,3 MD, MSc, PhD, Jean-Christophe Lecomte,2 MD, Eduardo Pedrolo-Silveira,1 MD, George Mendes,1 MD, Marie-Paule Boncoeur Martel,2 MD, Suzana Saleme,1 MD, MSc, and Charbel Mounayer,1,3 MD, PhD

Departments of 1Interventional Neuroradiology and 2Diagnostic Neuroradiology, Dupuytren University Hospital (CHU Limoges); and 3University of Limoges, CNRS, XLIM, UMR 7252, Limoges, France

OBJECTIVE Even though published data exist concerning the prevalence of ischemic lesions detected by diffusion-weighted imaging (DWI) following endovascular treatment of intracranial aneurysms, a single-center cross-evaluation of the different endovascular techniques has been lacking. The authors sought to prospectively evaluate the prevalence and clinical significance of ischemic lesions occurring after endovascular treatment of intracranial aneurysms and to compare the safety and effectiveness of a broad spectrum of currently accepted endovascular techniques in a single-center setting.METHODS This was a prospective cohort study involving consecutive patients treated for intracranial aneurysms exclu-sively by endovascular means, excluding treatments in the acute rupture phase, in a center featuring an endovascular-only treatment policy for intracranial aneurysms. All patients underwent MRI, including a 3-directional DWI sequence, before treatment, 24 hours postprocedure, and 6 months following endovascular embolization. Selective angiography was performed at 6 months’ follow-up.RESULTS From January 2012 through December 2013, 164 aneurysms were treated in 128 consecutive patients. En-dovascular techniques included coiling (14.6%), balloon-assisted coiling (20.1%), stent-assisted coiling (3.7%), low-profile stent-assisted coiling, flow diversion (38.4%), and very complex treatments (6.1%) involving 2 stents in Y or T configura-tions. On postprocedure MRI, the rates of occurrence of new DWI-positive lesions were 64.3% for coiling, 54.5% for remodeling, 61.1% for stent-assisted coiling, 53.7% for flow-diverting stents, and 75% for very complex treatments (p = 0.4962). The 6-month procedure-related morbidity and mortality rates were 6.25% and 0%, respectively. At 6 months’ follow-up, 93% of the patients had modified Rankin Scale (mRS) scores of 0–2. Very complex treatments offered a higher complete occlusion rate (100%) than all other techniques (66.7%–88.9%). Age and length of procedure were in-dependent factors for DWI lesion occurrence. The diameter of DWI lesions on 24-hour postprocedure MRI was positively correlated with mRS score at discharge. Among the DWI-positive lesions measuring less than 2 mm in diameter on the 24-hour MRI, 44.12% had regressed at 6 months.CONCLUSIONS Procedure-related DWI lesions are far more often encountered in silent forms than they are clinically evident. They do not seem to be significantly correlated with procedure-related complications, nor do they seem to im-pair clinical outcome, regardless of the endovascular technique. Small lesions (< 2 mm in diameter) may regress within 6 months. The use of the most adapted technique, in terms of aneurysm configuration, results in significant total occlusion rates, with acceptable safety.https://thejns.org/doi/abs/10.3171/2016.11.JNS161020KEY WORDS stents; intracranial aneurysm; endovascular treatment; coiling; flow diverter; MRI; vascular disorders

J Neurosurg Volume 128 • April 2018982 ©AANS 2018, except where prohibited by US copyright law

Unauthenticated | Downloaded 05/18/22 03:40 PM UTC

Endovascular aneurysm treatment with MRI evaluation

J Neurosurg Volume 128 • April 2018 983

Endovascular treatment strategies have been exten-sively improved during the last 2 decades, providing practitioners with technical alternatives for treat-

ing aneurysms that were considered, until recently, very challenging.22 The safety and effectiveness of the numer-ous endovascular techniques has been proven by several studies. Recently, the use of MRI as an adjunctive tool for ischemic event monitoring has revealed more procedure-related ischemic lesions than initially anticipated.6,13

Although silent or clinically evident ischemic lesions have been reported after endovascular aneurysm treatment in several studies, there has been, until now, no cohort study of exclusively endovascular, unselected intracranial aneurysms, treated by the same operators, with all major treatment strategies, including flow diversion and complex stent configurations such as X and Y stenting. The aim of this work was to prospectively evaluate the safety and effectiveness of a range of endovascular techniques in the treatment of unruptured intracranial aneurysms employ-ing prospectively acquired clinical, angiographic, and MRI data.

MethodsThis is a prospective cohort study of patients with un-

ruptured or recanalized intracranial aneurysms who were treated by endovascular means with a broad spectrum of technical approaches during a period of 24 months (from January 1, 2012, to December 31, 2013) in a university hospital that has adopted an endovascular-only policy for intracranial aneurysms. Institutional review board ap-proval was obtained from before data collection. Written consent was obtained from all patients before treatment.

Inclusion and Exclusion CriteriaConsecutive adult patients treated for one or more in-

tracranial aneurysms that were unruptured, recanalized, or ruptured but not in the acute phase were included. The therapeutic decision making was based on usual factors, including family history of aneurysm rupture, and per-sonal history, including prior aneurysm rupture or mul-tiple aneurysms, as well as personal willingness to receive treatment, expressed during consultation. The aim of the endovascular treatment was to achieve a complete occlu-sion of the aneurysm without recanalization during the follow-up. The technical complexity of each aneurysm was evaluated on the basis of the aspect and dome-to-neck ratios.8 Patients were excluded from the study if they re-fused or were unable to give consent, if MRI was con-traindicated, or if they were undergoing treatment for a ruptured intracranial aneurysm in the acute phase.

Endovascular TechniquesThe technical approaches were prospectively catego-

rized in 6 subgroups: coiling (including double micro-catheter), balloon-assisted coiling (including double re-modeling), stent-assisted coiling (including jailing and remodeling followed by conventional stenting), low-pro-file stent-assisted coiling (including jailing or balloon re-modeling with immediate stent deployment of a low-pro-file, braided stent), flow diversion (including jailing, use

of telescoping stents, Y or T configurations exclusively with flow diverters), and very complex treatments (Y, X, or T stenting with at least 1 conventional stent).

Very complex treatments were considered those involv-ing more than 1 stent, whether conventional, low-profile, flow diverter, or a combination, in complex configurations such as X and Y, excluding telescopic configuration; excep-tions were the Y and T configurations with 2 flow-diverter stents, which were categorized in the flow-diverter catego-ry due to the flow-diverting effect in the jailed artery.

Procedure-Related MedicationAll patients whose treatment strategy involved a stent

were treated with a daily regimen of 75 mg of Plavix (clop-idogrel) and 160 mg of aspirin, starting 6 days prior to the procedure and continuing for 6 months and 1 year, respec-tively; patients were tested for resistance to clopidogrel and to aspirin with the VerifyNow P2Y12 and VerifyNow Aspirin test (Accriva), respectively. In all of these cases, a platelet count over 100 × 109/L and hematocrit over 30% were confirmed before resistance testing in order to en-sure reliability of the results. Acceptable values for good response to antiplatelet therapy were P2Y12 reaction unit (PRU) values below 230 and aspirin reaction unit (ARU) values less than 550.

In cases of resistance to Plavix that persisted even after tripling the dose, alternative treatment strategies, such as balloon-assisted coiling or other non-stent treatment, were considered. At the time the study was conducted, prasug-rel and ticagrelor were not yet used in the department as alternative antiplatelet strategies.

Clinical Evaluation and OutcomesIn addition to the standard clinical evaluation for all

treated patients, which was performed by the principal interventional neuroradiologists who performed the in-terventions, all patients in the study also underwent addi-tional evaluations that were performed independently by 2 senior neurosurgeons (G.M. and E.P.-S.). They separately and independently examined the patients at the predefined time points and filled out an electronic questionnaire that was subsequently used in a blinded form for the statistical analysis.

The clinical evaluation time points were as follows: before treatment, 24 hours after treatment, between Day 3 and Day 5 after treatment in cases in which a flow-di-version stent was placed, at discharge from the hospital, and at 6-month follow-up evaluations. At each time point the cognitive state of the patients was evaluated with re-spect to orientation, language, calculation, memory, and visuospatial reproduction. Quantification and documenta-tion of the results was achieved by means of the Mini–Mental State Examination (MMSE). Functional outcome was documented by means of the modified Rankin Scale (mRS) for each time point.

Imaging EvaluationAll digital subtraction angiography (DSA) studies were

reviewed independently by 2 senior interventional neu-roradiologists (C.I. and C.M.). In case of discrepancy, a

Unauthenticated | Downloaded 05/18/22 03:40 PM UTC

C. Iosif et al.

J Neurosurg Volume 128 • April 2018984

decision was taken by consensus, after review of MRI and DSA studies. Four-axis superselective DSA was per-formed in every patient before treatment. The same proto-col was used for the follow-up angiography. Angiographic outcomes were categorized according to the Raymond-Roy23 or the O’Kelly-Marotta (OKM)18 grading scale, de-pending on the endovascular treatment used.

MRI data were reviewed independently by 2 diagnos-tic neuroradiologists (M.-P.B.M. and J.-C.L.), blinded as to the type of intervention. Scans were performed using a 3-T system (Achieva, Philips Medical Systems). Brain MRI protocol included a 3D diffusion-weighted imaging (DWI) sequence and a fluid-attenuated inversion recovery (FLAIR) sequence, as previously described.13 Every pa-tient had a brain MRI scan 12–24 hours before endovas-cular treatment, between 6 and 24 hours postprocedure, and 6 months following the procedure. In addition, pa-tients who underwent flow-diverter placement also had a brain MRI scan between posttreatment Days 3 and 5. MRI could also be performed on an emergency basis whenever clinical symptoms made it necessary.

Supplementary DataDuring a single calendar month (June 1–30, 2016), all

adult patients with scheduled selective intracranial an-giograms underwent an MRI scan before and at 24 hours post-DSA to evaluate the DWI lesion rate in diagnostic angiographies, as opposed to endovascular procedures.

Statistical AnalysisDescriptive statistics were applied after verifying nor-

mality by the Kolmogorov-Smirnov test for normal distri-bution (the Student t-test was used for normal distributions

and Wilcoxon’s test for nonnormal distributions). Fisher’s exact test and the Mann-Whitney test were used for quan-titative data, and the chi-square test was used for qualita-tive data. Multiple regression analysis was performed with respect to mRS score at discharge and DWI occurrence, using the “enter” method. Statistical analyses were per-formed with appropriate statistical electronic software (Statistica, StatSoft); the level of statistical significance was determined as p ≤ 0.05.

ResultsPatient Population

Over the course of a 24-month period (from January 1, 2012, to December 31, 2013), 164 intracranial aneurysms were treated in 143 endovascular procedures in 128 con-secutive patients (47 male [36.7%] and 81 female [63.3%]; mean age of 52.6 ± 12.2 years). In accordance with the ex-clusion criteria, 90 patients were excluded because the rel-evant procedures were performed on an emergency basis after an acute rupture of an intracranial aneurysm (Fig. 1).

Before treatment, 94 patients (73.4%) were asymptom-atic, 6 (4.7%) had experienced nonneurological clinical symptoms, 4 (3.1%) had neurological symptoms that re-solved after treatment, 22 (17.2%) had permanent neuro-logical deficits, and 2 (1.6%) had other symptoms. A total of 126 patients (98.4%) had mRS scores of 0–2 before treatment.

Resistance to Plavix that was not reversible with dose increase was found in 21 (16.4%) of the 128 patients. Per-sistent aspirin resistance was found in 4 (3%) and resistance to both was found in 1 patient (0.8%). Testing of P2Y12 inhibitor response was not deemed necessary and thus was

FIG. 1. Flowchart of patient cohort analysis for this study.

Unauthenticated | Downloaded 05/18/22 03:40 PM UTC

Endovascular aneurysm treatment with MRI evaluation

J Neurosurg Volume 128 • April 2018 985

not performed in 25 patients (19.5%) for whom the endo-vascular treatment strategy did not involve stenting.

Aneurysm CharacteristicsIn the 164 treated intracranial aneurysms, 162 were

saccular (98.8%) and 2 were fusiform (1.2%). In 117 cases (71.3%), the treatment was the first treatment for that an-eurysm, and 47 aneurysms were treated for a recanaliza-tion (28.7%). Most of the aneurysms (138 [84.1%]) were asymptomatic; 26 (15.9%) were symptomatic.

Of the 162 saccular aneurysms, 85 (53.1%) were small (diameter ≤ 5 mm), 63 (39.4%) were medium-sized (6–15 mm), 11 (6.9%) were wide (16–25 mm), and 1 (0.6%) was giant (> 25 mm). Twenty-six aneurysms were narrow-necked (15.9%) and 138 were wide-necked (84.1%, cor-responding to a dome-to-neck ratio < 2). The mean aspect ratio was calculated at 1.4 (95% CI 1.3–1.5) and the mean dome-to-neck ratio at 1.3 (95% CI 1.2–1.4).

Treatment and Technical OutcomesAll endovascular procedures were feasible. Ninety-nine

patients were treated for 1 aneurysm (77.3%), 26 for 2 an-eurysms (20.3%), 1 for 3 aneurysms (0.8%), and 2 for 5 aneurysms (1.6%). The treatment required 1 embolization session for 113 patients (88.3%) and 2 embolization ses-sions for 15 patients (11.7%).

Mean total procedural time was 116.7 ± 54.3 minutes. The mean total procedural time was longer in cases of multiple aneurysm treatment during the same emboliza-tion session (134.5 minutes, 95% CI of the mean 104.6–153.7) than in cases of single aneurysm treatment (102.0 minutes, 95% CI of the mean 94.2–109.8), and the differ-ence was statistically significant (p = 0.0289).

The technical approaches consisted of coiling for 24 aneurysms (14.6%), balloon-assisted coiling for 33 an-eurysms (20.1%), stent-assisted coiling for 6 aneurysms (3.7%), low-profile stent-assisted coiling for 28 aneurysms (17.1%), flow diversion for 63 aneurysms (38.4%), and very complex treatments for 10 aneurysms (6.1%). There was a

statistically significant correlation between the location of the treated aneurysm and the technique (c2 = 92.488, DF = 40, p < 0.0001) (Table 1).

A stent was deployed for 107 aneurysms (65.2%) with a mean (± SD) diameter of 3.5 ± 0.8 mm and an average length of 23.8 ± 9.8 mm. Stent deployment induced the coverage of at least 1 branch for 105 aneurysms (64.0%); the mean number of branches covered was 2.3 ± 1.2 branches. The covered branches arose from the convexity for 33.6%, orthogonally for 54.9%, from the concavity for 4.1%, and from the aneurysmal sac for 7.4%.

Immediate and Follow-Up Clinical OutcomesOf 128 patients, 115 (89.8%) had mRS scores of 0–2 at

24 hours postprocedure, 119 (93.0%) had mRS scores of 0–2 at discharge, and 123 (96.1%) had mRS scores of 0–2 at 6 months. The mRS scores are summarized in Table 2. Of the 73 patients treated with flow-diversion stents, 64 (87.7%) had mRS scores of 0–2 at the intermediate additional evaluation (between 3 and 5 days after treat-ment), with an intermediate mRS score of 0 for 44 patients (60.3%), 1 for 17 patients (23.3%), 2 for 3 patients (4.1%), 3 for 3 patients (4.1%), 4 for 1 patient (1.4%), and 5 for 5 patients (6.8%).

TABLE 1. Treatment technique by aneurysm location

Aneurysm Location Coiling BAC SAC LPSAC FD Very Complex Treatments Total

ACA (including ACoA) 4 4 1 16 10 2 37 (22.6)MCA 8 11 3 7 14 5 48 (29.3)Carotido-ophthalmic region 2 4 0 3 17 0 26 (15.9)PCoA 3 5 0 0 2 1 11 (6.7)AChA 0 0 1 0 2 0 3 (1.8)Carotid T junction 0 4 0 0 5 0 9 (5.5)Other parts of ICA 0 0 0 1 11 0 12 (7.3)BA 3 4 1 1 0 2 11 (6.7)Other parts of pst circulation (including

PCA, VA, PICA, AICA, & SCA)4 1 0 0 2 0 7 (4.3)

Total 24 (14.6) 33 (20.1) 6 (3.7) 28 (17.1) 63 (38.4) 10 (6.1) 164 (100)ACA = anterior cerebral artery; AChA = anterior choroidal artery; ACoA = anterior communicating artery; AICA = anterior inferior cerebellar artery; BA = basilar artery; BAC = balloon-assisted coiling; FD = flow diversion; ICA = internal carotid artery; LPSAC = low-profile stent-assisted coiling; MCA = middle cerebral artery; PCA = pos-terior cerebral artery; PCoA = posterior communicating artery; PICA = posterior inferior cerebellar artery; pst = posterior; SAC = stent-assisted coiling; SCA = superior cerebellar artery; VA = vertebral artery.Values are numbers of aneurysms (%); c² = 92.488, DF = 40, p < 0.0001.

TABLE 2. Modified Rankin Scale scores

mRS Score

Before Treatment

24 Hrs After Treatment

At Discharge

At 6 Mos

0 95/128 (74.2) 82/128 (64.1) 88/128 (68.8) 94/128 (73.4)1 23/128 (18.0) 22/128 (17.2) 20/128 (15.6) 16/128 (12.5)2 8/128 (6.3) 11/128 (8.6) 11/128 (8.6) 13/128 (10.2)3 2/128 (1.6) 9/128 (7.0) 8/128 (6.3) 2/128 (1.6)4 0/128 (0) 3/128 (2.3) 1/128 (0.8) 2/128 (1.6)5 0/128 (0) 1/128 (0.8) 0/128 (0) 0/128 (0)6 0/128 (0) 0/128 (0) 0/128 (0) 1/128 (0.8)

Values are numbers of patients (%).

Unauthenticated | Downloaded 05/18/22 03:40 PM UTC

C. Iosif et al.

J Neurosurg Volume 128 • April 2018986

Complications and Clinical ImpactFive aneurysm ruptures (3.0%), 1 branch perforation

(0.6%), and 6 inadvertent thrombus formations (3.6%) oc-curred during the procedure. There was no statistically significant difference in intraprocedural events among the different treatment techniques (c2 = 27.551, DF = 25, p = 0.32). After the procedure, new clinical symptoms were noted in association with DWI-positive lesions in 23 cases, and in 13 (10%) of 128 patients, they were evident as mod-ification of the mRS outcome at 24 hours after treatment. There was no early or delayed rupture, stent migration, or mass effect (perianeurysmal brain inflammatory reaction) for the whole cohort.

There was no statistically significant difference in in-traprocedural complications concerning single aneurysm (21/126 procedures, 16.7%) versus multiple aneurysm em-bolization session (4/25 procedures, 16.0%) (c2 = 5.232, DF = 5, p = 0.3883). There was no statistically significant dif-ference in procedure-related complications depending on the technique (c2 = 16.769, DF = 10, p = 0.0796) (Table 3).

The multiple regression analysis showed positive sta-tistically significant correlation regarding mRS score at discharge for the factors of age and total procedure time. Number of aneurysms treated at 1 session, first treatment or recanalization, technique, and resistance to aspirin, Plavix, or both were not retained as statistically significant factors (coefficient of determination [R2] 0.1398, adjusted R2 0.1061, multiple correlation coefficient 0.3739, residual SD 0.8614, p = 0.001).

Morbidity and MortalityThere was no procedure-related mortality (0%). One

(0.8%) of the 128 patients died 3 months after the proce-dure due to multiorgan failure, caused by acute pyelone-phritis that evolved into acute renal failure. This patient (Case 104) was a 75-year-old woman who underwent flow-diverter placement for treatment of a large left MCA aneu-rysm and had an mRS score of 0 at discharge. The overall procedure-related mortality rate in the cohort was thus 0.8%. The rate of procedure-related morbidity at discharge was 7.8% (10/128), and the rate of permanent procedure-re-lated morbidity at 6 months’ follow-up was 6.25% (8/128).

MRI OutcomesA postprocedure MRI study was performed in 105

(82.0%) of 128 patients. Among these 105 patients, 60 (57.1%) had at least 1 new DWI-positive lesion. There were no new DWI-positive lesions distal to the parent artery in 58 cases (55.2%); 1 or more new DWI-positive lesions

were found in 47 cases (44.8%). Distal to covered branch-es, MRI revealed 1 or more new DWI-positive lesions in 25 patients (23.8%). In the same axis territory (but exclud-ing the aforementioned lesions), 24 patients (22.9%) had 1 or more new DWI-positive lesions. In other territories, not involved by the embolization, at least 1 new DWI-positive lesion was detected in 6 patients (5.7%).

On the postprocedure MRI, there was no statistically significant difference in the frequency of new DWI-posi-tive lesions according to the chosen treatment technique, with rates of 64.3% for coiling, 54.5% for remodeling, 0% for stent-assisted coiling, 61.1% for low-profile stent-assist-ed coiling, 53.7% for flow-diversion stenting, and 75% for very complex treatments (c2 = 4.380, DF = 5, p = 0.4962).

Among 60 patients who had new DWI-positive le-sions on the postprocedure MRI, there were 9 procedure-related complications (6 ischemic events and 3 aneurysm ruptures). There was no statistically significant association between the discovery of new DWI-positive lesions on the postprocedure MRI and procedure-related complications (c2 = 2.393, DF = 2, p = 0.3023).

An intermediate MRI study was obtained in 57 (90.5%) of the 63 patients treated with a flow-diverter stent. Among those patients, 14 (24.6%) had at least 1 new DWI-positive lesion, 3 of which corresponded to procedure-related is-chemic complications (2%, 3/143). There was no statisti-cally significant association between the discovery of new DWI-positive lesions on the intermediate MRI and the presence of procedure-related complications (c2 = 1.408, DF = 2, p = 0.4946). Regarding DWI-positive lesions distal to the parent artery, 1 or more new lesions were found in 7 cases (12.3%). Distal to covered branches, 1 or more new DWI-positive lesions were found in 6 patients (10.5%); in the same axis, 2 patients (3.5%) had 1 or more new DWI-positive lesions.

Follow-up MRI studies were obtained at 6 months in 68 cases (53.1%). Among those 68 patients, 5 had at least 1 new ischemic lesion on FLAIR or DWI. Regarding FLAIR or DWI hyperintensities distal to the parent artery, there was no new FLAIR or DWI hyperintensity in 65 (95.6%) of 68 cases and 1 or more new FLAIR- or DWI-positive lesions in 3 cases (4.4%). Distal to covered branches, the MRI revealed 1 or more new FLAIR- or DWI-positive le-sions in 1 (1.5%) of 68 patients. In the same axis territory (but excluding the aforementioned lesions), 2 (2.9%) of 68 patients had 1 or more new FLAIR- or DWI-positive le-sions.

Overall, at 6 months, 30 (44.12%) of the 68 patients with DWI-positive lesions did not have either new DWI

TABLE 3. Procedure-related complications according to the technique used

Procedure-Related ComplicationsTechnique

TotalCoiling BAC SAC LPSAC FD Complex Techniques

Absence of complication 22 28 4 23 55 7 139 (84.8)Ischemic complications 0 3 2 5 8 3 21 (12.8)Intraprocedural aneurysm rupture 2 2 0 0 0 0 4 (2.4)Total 24 (14.6) 33 (20.1) 6 (3.7) 28 (17.1) 63 (38.4) 10 (6.1) 164

Values are numbers of aneurysms (%); c² = 16.769, DF = 10, p = 0.0796, contingency coefficient = 0.305.

Unauthenticated | Downloaded 05/18/22 03:40 PM UTC

Endovascular aneurysm treatment with MRI evaluation

J Neurosurg Volume 128 • April 2018 987

lesions or FLAIR hyperintensities corresponding to the DWI lesions documented in the 24-hour postprocedure MRI. The mean diameter of the lesions that regressed was 1.3 ± 0.6 mm. The mean diameter value for the DWI le-sions that were clinically evident as complications was 6.3 ± 2.2 mm, and they were all evident as high–signal inten-sity lesions on FLAIR at 6 months. The diameter of DWI lesions on 24-hour postprocedure MRI was positively cor-related with mRS score at discharge (R2 0.2606, residual SD 0.8803, p < 0.001).

There was no statistically significant difference between the techniques of treatment with respect to the occurrence of new FLAIR- or DWI-positive lesions at 6 months, with rates of 11.1% for coiling, 8.3% for remodeling, 0% for stent-assisted coiling, 0% for low-profile stent-assisted coiling, 11.5% for flow-diversion stenting, and 0% for very complex treatments (c2 = 1.968, DF = 5, p = 0.8536).

Multiple regression analysis showed that total proce-dure time, age, and aspirin resistance were independent factors of occurrence of new DWI lesions at 24 hours postintervention. Number of treated aneurysms in 1 ses-sion, technique, and clopidogrel resistance were not re-tained as significant (zero-order correlation coefficient [r] for total procedural time 0.06270, age r -0.03055, aspirin resistance r -0.04463; R2 0.03005, adjusted R2 -0.03186, multiple correlation coefficient 0.1733, residual SD 1.1871).

Angiographic OutcomesThe Raymond-Roy classification was used for 101

(61.6%) of 164 aneurysms. There was a good correlation between the 6-month angiographic outcomes and the postprocedure results (p < 0.0001). The O’Kelly-Marotta

(OKM) classification was used for 63 aneurysms (38.4%), and for these lesions also, there was a good correlation be-tween the 6-month angiographic outcomes and the post-procedure results (p < 0.0041). Angiographic outcomes are summarized in (Table 4).

On 6-month follow-up DSA, for the 100 aneurysms evaluated by the Raymond-Roy classification, there was a higher rate of complete occlusion in cases of retreatment after a partial recanalization than in cases of initial treat-ment, but the difference was not statistically significant (c2 = 3.755, DF = 2, p = 0.1530). Similarly, for the aneurysms evaluated by the OKM grading scale, there was a higher rate of Grade D (no filling) in cases of retreatment after a partial recanalization than in cases of initial treatment, but the difference was not statistically significant (c2 = 2.401, DF = 2, p = 0.3011).

In the global aneurysm evaluation scale, a higher rate of complete occlusion was found in cases of retreatment (89.4%, 42 of 47 treated aneurysms) than in cases of initial treatment (78.5%, 92 of 117), but the difference was not statistically significant (chi-square = 3.668, DF = 2, p = 0.1598). On 6-month follow-up DSA, very complex treat-ments showed a higher rate of complete occlusion than other techniques, but the difference was not statistically significant (c2 = 9.971, DF = 10, p = 0.4430).

Supplementary DataDuring 1 calendar month, 38 selective intracranial

DSAs were performed in 38 adult patients (13 men, 25 women), with mean age of 49.8 ± 10.5 years. Seven (18.7%) of these 38 patients were found to have punctate DWI le-sions, all measuring less than 2 mm in diameter. None was symptomatic post-DSA, and none showed modification in the post-DSA MMSE. The prevalence of punctate DWI le-sions was significantly greater in the treatment cohort than in the diagnostic DSA group (c2 = 6.121, DF = 1, p = 0.01).

DiscussionTo the best of our knowledge, this is the first single-

center cohort study of intracranial aneurysms exclusively treated by endovascular means, with several simple and complex techniques, for which a prospective MRI investi-gation was implemented. Even though regression of ische-mic DWI-positive lesions has already been described,2 it has not previously been clearly demonstrated with a cohort study. In the present study 44% of the small DWI lesions had regressed at 6 months; this was, however, not the case for any of the larger lesions of 5 mm or more. Moreover, small lesions were not related to clinical complications or poor clinical outcomes.

In a very recent study, Park et al.19 reported that mul-tiple aneurysms and the use of an Enterprise stent were independent factors for DWI lesion occurrence. In our study presented here, technique, multiple aneurysm treat-ments at a single session, and aneurysm localization were not retained as independent factors for poor clinical out-come at discharge. In contrast, length of intervention and age were independent factors for increased mRS scores at discharge.

The regression analysis in the study by Park and col-

TABLE 4. Angiographic outcomes

Angiographic OutcomeNo. of Cases (%)

Postprocedure At 6 Mos

Raymond-Roy (if no FD) Class 1 = complete occlusion 75 (74.3) 83 (83.0) Class 2 = residual neck 20 (19.8) 14 (14.0) Class 3 = residual aneurysm 6 (5.9) 3 (3.0) Total 101 (100) 100 (100)OKM (if FD) Grade D = no filling 6 (9.5) 50 (79.4) Grade C (1, 2, or 3) = entry remnant 17 (27.0) 10 (15.9) Grade B (1, 2, or 3) = subtotal filling 30 (47.6) 3 (4.8) Grade A (1, 2, or 3) = total filling 10 (15.9) 0 (0) Total 63 (100) 63 (100)Merged grading scales: Raymond-Roy

& OKM Complete occlusion = Class 1 +

Grade D133 (81.6)

Residual neck = Class 2 + Grade C

24 (14.7)

Residual aneurysm = Class 3 + Grade B + Grade A

6 (3.7)

Total 163 (100)

Unauthenticated | Downloaded 05/18/22 03:40 PM UTC

C. Iosif et al.

J Neurosurg Volume 128 • April 2018988

leagues19 showed that the occurrence of DWI lesions was positively correlated with age, with aspirin resistance, and with the length of the procedure. Interestingly, our results are in accordance with these data regarding antiaggrega-tion therapy (Plavix in this case), which was not retained as a predisposing factor in either study.

In our cohort, an important percentage of small-diam-eter DWI lesions regressed over time. This fact is clearly depicted for the first time after endovascular treatments, even though it is well known that DWI lesions can regress in patients who have suffered ischemic strokes. This ob-servation may partially explain the high percentage of silent lesions compared with those clinically expressed. Moreover, the results of this study show that the diameter of a DWI lesion on immediate postprocedure MRI is cor-related with clinical outcome.

In this cohort, treatment strategies were determined on a case-by-case basis in order to obtain optimal and stable results, with good clinical outcomes. Even though simple coiling is an excellent tool for the treatment of acutely rup-tured aneurysms, due to its technical simplicity and lack of need for antiplatelet treatment, its effectiveness for un-ruptured aneurysms is severely limited by an important recanalization rate.9 In the present series, standard coiling was used only for 14.6% of unruptured intracranial aneu-rysms; for 86.4% of the cases more advanced techniques were deemed appropriate.

The remodeling technique17 and its more complex vari-ants allow for endovascular treatment of wide-necked aneurysms and bifurcation aneurysms with complex or challenging configurations. According to the ATENA21 investigators, comparable safety rates were found for bal-loon-assisted coiling and simple coiling.20 In a literature review by Shapiro et al.,25 remodeling was more effective than coiling in terms of angiographic outcomes. Our re-sults are consistent with these findings, with remodeling demonstrating greater effectiveness than simple coiling.

Stent-assisted coiling techniques offer an alternative to remodeling for the endovascular treatment of wide-necked aneurysms and large and giant aneurysms.16,29 In addition, stent-assisted coiling is useful for fusiform and dissecting aneurysms.30 A literature review26 on intracranial stenting reported high immediate and follow-up angiographic oc-clusion rates but highlighted the presence of a “learning curve,” with significantly higher morbidity and mortality rates for the first 10 patients treated with stents than for patients treated subsequently. A recent multicenter pro-spective study11 on open-cell, self-expanding nitinol stents showed acceptable complication rates, with good angio-graphic and clinical outcomes.

The emergence of low-profile stents for intracranial aneurysm treatment, especially at distal or complex loca-tions, deployed usually after coiling, has provided another important tool for neurointerventionalists. With very high immediate-term total occlusion rates, while also preserv-ing safety, these devices have been increasingly used in the last 3 years, especially in distal locations, with very promising follow-up anatomical results.1,7

The results of our series are consistent with the pub-lished data, demonstrating superiority of stent treatment over standard coil embolization, with higher complete oc-

clusion rates and lower recanalization rates. In this cohort, complication rates remained acceptable. At the same time, the results of this series are in line with newer data that came to light recently and show comparable safety profiles for balloon-assisted versus simple coiling techniques24 and low rates of ischemic events for stent-assisted coiling of unruptured aneurysms.15

The use of flow-diverter stents represents a new para-digm5 in the endovascular treatment of intracranial an-eurysms. These devices are particularly useful in the management of the most complex configurations, such as multiple aneurysms in the setting of segmental arterial dissection, very small aneurysms (including blister-like le-sions),13,32,33 and large and fusiform aneurysms,10,27 but they are also useful in cases of aneurysm recanalization after initial coiling. This series highlights the relevance of flow-diversion stents in these indications, especially for aneu-rysm recanalization.

A recent study by Iosif et al.13 reported a higher occur-rence of silent ischemic lesions than expected. Transient symptoms were reported, usually around a month after the procedure, mainly in territories corresponding to covered branches of terminal type of circulation. These findings did not correlate with higher complication rates than the average accepted in the published literature for endovas-cular treatment of intracranial aneurysms. The findings of this study further support this conclusion.

In the current study, absence of delayed rupture was observed in the flow-diverter group. Nevertheless, longer follow-up was necessary to obtain complete aneurysm oc-clusion in patients treated with flow diversion, compared to those treated with the other techniques; this is the reason why an important improvement in angiographic results at 6 months was observed, as compared with the other tech-niques.

Wide-necked bifurcation aneurysms are considered challenging for endovascular treatment, since it may prove difficult to simultaneously protect both branches from coil migration. In such configurations, the use of more than 1 device, as in Y stenting,4,31 may prove to be useful in the hands of experienced practitioners. In the experience de-scribed in the present paper, Y and T stenting techniques were used in 10 patients (6.1%). In the cases presented herein, the rate of complete occlusion at 6 months was higher than in the literature (100%) (Fig. 2), with accept-able procedure-related complication rates, in line with other published data.31

We did not find any statistically significant correlation between the type of technique used and clinical outcome in this study. Nevertheless, we did find higher intraproce-dural rupture rates in the coiling and remodeling groups, as opposed to the stent, flow diverter, and complex tech-niques, although the difference was not statistically signif-icant. In contrast, more ischemic complications occurred in the groups in which a stent was used, conventional or flow diverter. The more complex the technique used, the higher the total occlusion rates were. Higher procedure times were observed for procedures in which more than 1 aneurysm was treated during a single session, but there was no associated increase in the rate of complications.

Regarding DWI-positive lesions on postprocedure

Unauthenticated | Downloaded 05/18/22 03:40 PM UTC

Endovascular aneurysm treatment with MRI evaluation

J Neurosurg Volume 128 • April 2018 989

imaging, all groups exhibited similar percentages, with slightly higher percentages within the complex technique group. Unlike previous studies, this study showed no sta-tistically significant difference in the rate of DWI-positive lesions in patients treated with flow diversion compared to those treated with other endovascular techniques. Also, in contrast to previous studies in which relatively lower DWI findings were reported in patients treated with coiling6 or balloon remodeling techniques,3 in this series these find-ings occurred more often in patients treated with these techniques. Apart from the fact that previous series were limited in number, we attribute the difference in our find-ings to our use of 3-T MRI, which probably allows for more punctate lesions to be identified.

In accordance with our results, stent-assisted coiling was found to be comparable to simple coiling with re-spect to the incidence of DWI-positive lesions in a recent

study.12 We attribute the comparable rates of DWI lesions among the stent versus no-stent treatment groups in our study to the fact that, in this cohort, patients with Plavix resistance that could not be corrected with dose increase were switched over from flow diverter or stent treatment to balloon-assisted coiling or simple coiling, if that was feasible. Indeed, in a recent study, 48.3% of clopidogrel-resistant patients treated with simple coiling were found to have lesions on DWI.14

Whether they are of thromboembolic or hemodynamic origin, or even, as a recent publication suggested, originat-ing from endothelial cells circulating after endovascular treatment,28 small-sized DWI-positive lesions associated with endovascular treatment for unruptured aneurysms do not seem to increase clinical ischemic complications. With careful patient and strategy selection as well as effective antiplatelet therapy, and considering the variety of tech-

FIG. 2. Images obtained in a 73-year-old woman treated for a basilar tip aneurysm. A and B: 3D rotational angiography recon-struction (A) and selective DS angiogram (B) from the left vertebral artery, respectively, showing the wide-necked aneurysm with a small bleb on its dome. The aneurysm was treated with double Y stenting and coiling. C: DS angiogram obtained immediately after the procedure, showing complete exclusion of the aneurysm and patent posterior cerebral and anterior inferior cerebellar ar-teries. D and E: 3D rotational angiography reconstruction (D) of the double stenting before coiling and posttreatment single-shot image (E). F: Six-month control showing complete exclusion of the aneurysm. G–I: Axial DW (G and I) and FLAIR (H) images obtained immediately after treatment (G) and at 6 months’ follow-up (H and I), showing absence of ischemic complications or DWI spots. Figure is available in color online only.

Unauthenticated | Downloaded 05/18/22 03:40 PM UTC

C. Iosif et al.

J Neurosurg Volume 128 • April 2018990

nical approaches available today, endovascular treatments seem to be safe and effective, with good clinical outcomes and acceptable complication rates.

The results of the present study suggest that the underly-ing pathophysiological mechanisms of DWI lesions related to endovascular treatments are more complex than initially thought. Some of them seem to regress, while others prog-ress to infarcts. They are more frequent than clinically ex-pected, often subclinical, and sometimes delayed. These facts suggest that probably more than 1 mechanism is re-lated to what we document as DWI lesions after endovas-cular treatment. This discrepancy between clinical exami-nation and MRI findings should be further investigated to elucidate the pathophysiological nature of the DWI lesions and the underlying mechanisms related to their formation and behavior.

LimitationsEven though a priori power analysis was conducted for

the study population, its division into several subgroups ac-cording to treatment limits statistical power. Nevertheless, the results are valuable, especially since the same operators performed all the treatments, thus allowing for the com-parison of the different techniques. This protocol is still in place, and we plan to acquire a larger study population for further statistical analysis using a 5-year cutoff.

Lack of platelet testing for the treatments not involving a stent remains a source of bias in the study; the coil-treated subgroup included patients both nonresistant and resistant to antiaggregation therapy. Similar to other neurovascular centers, the pharmaceutical treatment protocol for patients amenable to simple coiling in this study did not require pre- or postprocedural antiaggregation therapy. All coil-treated patients systematically received weight-adjusted doses of intravenously administered heparin as well as 250 mg of aspirin administered through the nasogastric cathe-ter during treatment. We preferred to convert the treatment to coiling for patients with antiplatelet resistance who were initially considered for stent treatment, while patients for whom simple coiling was planned all along were not tested for resistance to Plavix. To the best of our knowledge, the conversion of resistant cases to simple coiling is a com-mon practice in several neuroendovascular centers, and even though this practice produces a systemic bias for the study, it can be considered acceptable, given the fact that technical complications requiring antiaggregation therapy did not occur in this subgroup.

ConclusionsDWI-positive lesions are far more common than clini-

cally anticipated, regardless of the endovascular treatment technique, but they do not seem to be related to high com-plication rates. More than one-third of small DWI lesions identified on early posttreatment imaging may regress within 6 months. Appropriate technique selection results in acceptable complication rates, regardless of the technique used, with excellent anatomical outcomes. Very complex techniques, such as Y stenting, yield better angiographic outcomes, while still maintaining acceptable complication rates.

References 1. Akmangit I, Aydin K, Sencer S, Topcuoglu OM, Topcuoglu

ED, Daglioglu E, et al: Dual stenting using low-profile LEO baby stents for the endovascular management of challenging intracranial aneurysms. AJNR Am J Neuroradiol 36:323–329, 2015

2. Albach FN, Brunecker P, Usnich T, Villringer K, Ebinger M, Fiebach JB, et al: Complete early reversal of diffusion-weighted imaging hyperintensities after ischemic stroke is mainly limited to small embolic lesions. Stroke 44:1043–1048, 2013

3. Albayram S, Selcuk H, Kara B, Bozdag E, Uzma O, Kocer N, et al: Thromboembolic events associated with balloon-assist-ed coil embolization: evaluation with diffusion-weighted MR imaging. AJNR Am J Neuroradiol 25:1768–1777, 2004

4. Bartolini B, Blanc R, Pistocchi S, Redjem H, Piotin M: “Y” and “X” stent-assisted coiling of complex and wide-neck in-tracranial bifurcation aneurysms. AJNR Am J Neuroradiol 35:2153–2158, 2014

5. Becske T, Kallmes DF, Saatci I, McDougall CG, Szikora I, Lanzino G, et al: Pipeline for uncoilable or failed aneurysms: results from a multicenter clinical trial. Radiology 267:858–868, 2013

6. Biondi A, Oppenheim C, Vivas E, Casasco A, Lalam T, Sourour N, et al: Cerebral aneurysms treated by Guglielmi detachable coils: evaluation with diffusion-weighted MR im-aging. AJNR Am J Neuroradiol 21:957–963, 2000

7. Brasiliense LB, Yoon JW, Orina JN, Miller DA, Tawk RG, Hanel RA: A reappraisal of anterior communicating artery aneurysms: a case for stent-assisted embolization. Neurosur-gery 78:200–207, 2016

8. Brinjikji W, Cloft HJ, Kallmes DF: Difficult aneurysms for endovascular treatment: overwide or undertall? AJNR Am J Neuroradiol 30:1513–1517, 2009

9. Ferns SP, Sprengers ME, van Rooij WJ, Rinkel GJ, van Rijn JC, Bipat S, et al: Coiling of intracranial aneurysms: a sys-tematic review on initial occlusion and reopening and retreat-ment rates. Stroke 40:e523–e529, 2009

10. Fischer S, Perez MA, Kurre W, Albes G, Bäzner H, Henkes H: Pipeline embolization device for the treatment of intra- and extracranial fusiform and dissecting aneurysms: initial experience and long-term follow-up. Neurosurgery 75:364–374, 2014

11. Gentric JC, Biondi A, Piotin M, Mounayer C, Lobotesis K, Bonafé A, et al: Safety and efficacy of neuroform for treat-ment of intracranial aneurysms: a prospective, consecu-tive, French multicentric study. AJNR Am J Neuroradiol 34:1203–1208, 2013

12. Hahnemann ML, Ringelstein A, Sandalcioglu IE, Goericke S, Moenninghoff C, Wanke I, et al: Silent embolism after stent-assisted coiling of cerebral aneurysms: diffusion-weighted MRI study of 75 cases. J Neurointerv Surg 6:461–465, 2014

13. Iosif C, Camilleri Y, Saleme S, Caire F, Yardin C, Ponomar-jova S, et al: Diffusion-weighted imaging-detected ischemic lesions associated with flow-diverting stents in intracranial aneurysms: safety, potential mechanisms, clinical outcome, and concerns. J Neurosurg 122:627–636, 2015

14. Kim B, Kim K, Jeon P, Kim S, Kim H, Byun H, et al: Thromboembolic complications in patients with clopidogrel resistance after coil embolization for unruptured intracranial aneurysms. AJNR Am J Neuroradiol 35:1786–1792, 2014

15. Lessne ML, Shah P, Alexander MJ, Barnhart HX, Powers CJ, Golshani K, et al: Thromboembolic complications after Neu-roform stent-assisted treatment of cerebral aneurysms: the Duke Cerebrovascular Center experience in 235 patients with 274 stents. Neurosurgery 69:369–375, 2011

16. Mericle RA, Lanzino G, Wakhloo AK, Guterman LR, Hop-kins LN: Stenting and secondary coiling of intracranial

Unauthenticated | Downloaded 05/18/22 03:40 PM UTC

Endovascular aneurysm treatment with MRI evaluation

J Neurosurg Volume 128 • April 2018 991

internal carotid artery aneurysm: technical case report. Neu-rosurgery 43:1229–1234, 1998

17. Moret J, Cognard C, Weill A, Castaings L, Rey A: The “re-modelling technique” in the treatment of wide neck intracra-nial aneurysms. Angiographic results and clinical follow-up in 56 cases. Interv Neuroradiol 3:21–35, 1997

18. O’Kelly CJ, Krings T, Fiorella D, Marotta TR: A novel grad-ing scale for the angiographic assessment of intracranial aneurysms treated using flow diverting stents. Interv Neuro-radiol 16:133–137, 2010

19. Park JC, Lee DH, Kim JK, Ahn JS, Kwun BD, Kim DY, et al: Microembolism after endovascular coiling of unruptured cerebral aneurysms: incidence and risk factors. J Neurosurg 124:777–783, 2016

20. Pierot L, Spelle L, Leclerc X, Cognard C, Bonafé A, Moret J: Endovascular treatment of unruptured intracranial aneu-rysms: comparison of safety of remodeling technique and standard treatment with coils. Radiology 251:846–855, 2009

21. Pierot L, Spelle L, Vitry F: Immediate clinical outcome of patients harboring unruptured intracranial aneurysms treated by endovascular approach: results of the ATENA study. Stroke 39:2497–2504, 2008

22. Raper DM, Crowley RW, Liu KC, Starke RM: Endovascular techniques and devices for the treatment of intracranial aneu-rysms: a review of neurointerventional outcomes. J Neuro-surg Sci 60:104–115, 2016

23. Roy D, Milot G, Raymond J: Endovascular treatment of un-ruptured aneurysms. Stroke 32:1998–2004, 2001

24. Santillan A, Gobin YP, Mazura JC, Meausoone V, Leng LZ, Greenberg E, et al: Balloon-assisted coil embolization of intracranial aneurysms is not associated with increased periprocedural complications. J Neurointerv Surg 5 (Suppl 3):iii56–iii61, 2013

25. Shapiro M, Babb J, Becske T, Nelson PK: Safety and efficacy of adjunctive balloon remodeling during endovascular treat-ment of intracranial aneurysms: a literature review. AJNR Am J Neuroradiol 29:1777–1781, 2008

26. Shapiro M, Becske T, Sahlein D, Babb J, Nelson PK: Stent-supported aneurysm coiling: a literature survey of treatment and follow-up. AJNR Am J Neuroradiol 33:159–163, 2012

27. Topcuoglu OM, Akgul E, Daglioglu E, Topcuoglu ED, Peker A, Akmangit I, et al: Flow diversion in middle cerebral ar-tery aneurysms: is it really an all-purpose treatment? World Neurosurg 87:317–327, 2016

28. Vendrell JF, Cezar R, Kuster N, Lobotesis K, Costalat V, Machi P, et al: Endovascular treatment of unruptured intra-cranial aneurysms and circulating endothelial cells. Eur J Radiol 82:671–679, 2013

29. Wakhloo AK, Lanzino G, Lieber BB, Hopkins LN: Stents for intracranial aneurysms: the beginning of a new endovascular era? Neurosurgery 43:377–379, 1998

30. Wakhloo AK, Mandell J, Gounis MJ, Brooks C, Linfante I, Winer J, et al: Stent-assisted reconstructive endovascular re-pair of cranial fusiform atherosclerotic and dissecting aneu-rysms: long-term clinical and angiographic follow-up. Stroke 39:3288–3296, 2008

31. Yavuz K, Geyik S, Cekirge S, Saatci I: Double stent-assisted coil embolization treatment for bifurcation aneurysms: im-mediate treatment results and long-term angiographic out-come. AJNR Am J Neuroradiol 34:1778–1784, 2013

32. Yavuz K, Geyik S, Saatci I, Cekirge HS: Endovascular treat-ment of middle cerebral artery aneurysms with flow modi-fication with the use of the pipeline embolization device. AJNR Am J Neuroradiol 35:529–535, 2014

33. Zanaty M, Chalouhi N, Tjoumakaris SI, Gonzalez LF, Rosen-wasser R, Jabbour P: Flow diversion for complex middle ce-rebral artery aneurysms. Neuroradiology 56:381–387, 2014

DisclosuresThe authors report no conflict of interest concerning the materi-als or methods used in this study or the findings specified in this paper.

Author ContributionsConception and design: Mounayer. Acquisition of data: Iosif, Lecomte, Mendes, Pedrolo-Silveira, Saleme. Analysis and inter-pretation of data: all authors. Drafting the article: Iosif. Critically revising the article: Iosif, Mounayer. Reviewed submitted version of manuscript: Iosif. Statistical analysis: Iosif. Study supervision: Iosif, Mounayer.

CorrespondenceChristina Iosif, 2 Avenue Martin Luther King, Limoges 87042, France. email: christina.iosif@gmail.com.

Unauthenticated | Downloaded 05/18/22 03:40 PM UTC