C. Iosif and C. Mounayer
Department of Interventional Neuroradiology
Dupuytren University Hospital
Limoges, France

We read with interest the recent publication by Caroff et al¹ on saccular MCA aneurysm treatment by flow diverters (FDs), in regard to the increasing tendency to use FDs in distal, off-label localizations. We appreciate their important contribution to the subject but remain reserved regarding their strong conclusion. The subject is still under research, but some promising clinical and angiographic outcomes have been published.² We were slightly perplexed by the interpretation of the reported complication rate, taking into account the methodologic limitations of the study due to the small number of subjects.

Various mechanisms of ischemic complications are implicated in flow diversion with covered arteries, which are not always sufficiently represented in a small case series. Thrombosis related to an ineffective anti-aggregation regimen, suboptimal stent apposition on the arterial wall, or distal emboli provoked by the mechanical manipulations inside the arteries are types of complications that should not be confounded with the pure hemodynamic effect of flow diversion on a covered branch. Good discrimination of the various potential ischemic mechanisms is mandatory to obtain a more profound understanding of FD-related complications.

To clear a misunderstanding, we must comment on the complication rates of the case series by Saleme et al³ cited in the discussion. The overall complication rate for the MCA cases in the study was 5% (n = 1/19), with a sole side branch–related complication in the MCA aneurysm sub-series. Apart from reporting complication rates, they performed a classification of jailed branches, dividing them into anastomotic or terminal. In this section, a symptomatic angiographic change was defined as any angiographic remodelling at 6 months in patients who reported transient symptoms at any point during the follow-up of 6 months.

These findings, reported in the postprocedural period analysis, usually occurred around 3–4 weeks after stent placement and consisted of either transient symptoms or silent DWI spots. They were reported to delineate the progressive remodelling of jailed branches, as part of the collateral network development of the brain⁴ in the postprocedural period. They were described in patients under effective antiaggregation and should not be confounded with early ischemic findings in patients with inefficient antiaggregation or with immediate flow restriction in the jailed branches, related to local high metal coverage or stent-deployment defects.

The complications reported in the study of Caroff et al¹ were encountered in the immediate postprocedural period; as they mentioned, the complications seemed to be related mainly to antiaggregation and technical issues. These results are useful to plan further, larger scale studies; they should also be kept in mind in everyday practice. Controlled hypertension in the postprocedural period, avoidance of under- or overinhibition of P2Y12 receptors,² and slight device oversizing are key technical points to consider when covering MCA branches.

The use of FDs in MCA bifurcations is still under research; various parameters need to be clarified and standardized before establishing a consensus for this treatment. Jailing distal terminal intracranial branches such as MCA bifurcations remains a challenging issue, but with a careful hemodynamic case-by-case study and proper patient preparation, FD treatment in such cases may prove to be a useful technique in otherwise challenging complex cases. Further research is underway regarding this subject by several teams; until concrete data see the light, every conclusion should be taken with a grain of salt.

References

1. Caroff J, Neki H, Mihalea C, et al. Flow-diverter stents for the treatment of saccular middle cerebral artery bifurcation aneurysms. AJNR Am J Neuroradiol 2015 Sep 24. [Epub ahead of print]
2. Kallmes DF, Hanel R, Lopes D, et al. International retrospective study of the Pipeline embolization device: a multicenter aneurysm treatment study. AJNR Am J Neuroradiol 2015;36:108–15
3. Saleme S, Iosif C, Ponomarjova S, et al. Flow-diverting stents for intracranial bifurcation aneurysm treatment. Neurosurgery 2014;75:623–31; quiz 631
4. Rouchaud A, Leclerc O, Benayoun Y, et al. Visual outcomes with flow-diverter stents covering the ophthalmic artery for treatment of internal carotid artery aneurysms. AJNR Am J Neuroradiol 2015;36:330–36

Reply

J. Caroff, L. Spelle and J. Moret
Department of Interventional Neuroradiology
Hôpital Bicêtre, Assistance Publique des Hôpitaux de Paris, Paris Sud Université
Paris, France

We would like to comment on the letter to the Editor regarding our article “Flow-Diverter Stents for the Treatment of Saccular Middle Cerebral Artery Bifurcation Aneurysms.”¹ We thank Dr Iosif and colleagues for their interest in our work, and we welcome the opportunity to comment on some of their remarks. First, we agree that there are multiple mechanisms involved in thromboembolic complications when using flow-diverter stents (FDSs) and that in some cases, the mechanisms can be unclear. However, we would strongly assert that in our study, complications were almost exclusively related to hemodynamic effects and not due to any technical issues, as suggested in the letter of Dr Iosif and colleagues.

No cases of thrombosis related to ineffective antiaggregation therapy were encountered because all patients were tested for any potential aspirin or clopidogrel resistance with the VerifyNow P2Y12 assay (Accumetrics, San Diego, California) and hematologic lab tests, as performed by Saleme et al.² We admit the possibility that even without biologic resistance to clopidogrel, this medication may be insufficient in those cases in which the covered branch is at very high risk of occlusion due to sudden flow restriction in the first hours after FDS delivery. Therefore, we as a department are considering a switch from clopidogrel to ticagrelor.³

Stent apposition is much easier to obtain at sites of middle cerebral artery bifurcation aneurysms than at sites of carotid siphon aneurysms due to less tortuosity. In addition, in our study, stent apposition was always confirmed with postoperative VasoCT (Philips Healthcare, Best, the Netherlands). If required, FDSs were ballooned to achieve a perfect opening.

Using diffusion-weighted MR imaging, we did not detect any distal emboli in the FDS branch provoked by mechanical manipulations during FDS delivery. In fact, in most cases branch catheterization and FDS positioning were quite simple at these locations.

In addition to these points, blood pressure was strictly controlled during treatment and in an intensive care unit for 12 hours after treatment.

We apologize for any eventual inaccuracies in the analysis of the complication ratio in the study by Saleme et al.² Because we tried to focus only on MCA saccular aneurysms, we excluded all blister aneurysms; this exclusion may have resulted in an overestimation of the morbidity rate from the available data in this study. However, we remain convinced that the use of FDS for the treatment of saccular MCA bifurcation aneurysms carries a risk of complications. As reported and discussed by Saleme et al, in some cases, ischemic complications will occur in the covered branch territory because the corticopial anastomosis is unable to fully meet the needs of the brain area. However, how to predict this phenomenon from digital subtraction angiography data (even with balloon test occlusion) is not yet clearly understood. Moreover, in our studies, DWI ischemic findings are seen in 43% of cases.

We wish to encourage Iosif and colleagues in their research to clarify the mechanisms of branch modifications with flow diversion; there may be a place for FDSs in the management of lesions that are challenging for surgical clipping and endovascular treatment such as blood blister-like, fusiform MCA aneurysms or difficult, dysplastic, extremely broad-based aneurysms. However, in the case of saccular MCA bifurcation aneurysms, because a meta-analysis from published studies with FDSs showed permanent deficit rates in 10.3% of cases (7/68),^1,2,4,5 we consider that under the conditions described in the different studies, FDSs are indeed not a “suitable solution” and other endovascular or surgical strategies should be preferred. Therefore, we encourage the rigorous evaluation of last-generation braided stents and new innovative devices that are increasingly becoming available on the market.

References

1. Caroff J, Neki H, Mihalea C, et al. Flow-diverter stents for the treatment of saccular middle cerebral artery bifurcation aneurysms. AJNR Am J Neuroradiol 2015 Sep 24. [Epub ahead of print]
2. Saleme S, Iosif C, Ponomarjova S, et al. Flow-diverting stents for intracranial bifurcation aneurysm treatment. Neurosurgery 2014;75:623–31; quiz 631
3. Storey RF, Angiolillo DJ, Patil SB, et al. Inhibitory effects of ticagrelor compared with clopidogrel on platelet function in patients with acute coronary syndromes: the PLATO (PLATelet inhibition and patient Outcomes) PLATELET substudy. J Am Coll Cardiol 2010;56:1456–62
4. Yavuz K, Geyik S, Saatci I, et al. Endovascular treatment of middle cerebral artery aneurysms with flow modification with the use of the Pipeline embolization device. AJNR Am J Neuroradiol 2014;35:529–35
5. Briganti F, Delehaye L, Leone G, et al. Flow diverter device for the treatment of small middle cerebral artery aneurysms. J Neurointerv Surg 2015 Jan 20. [Epub ahead of print]