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Treatment of blood blister aneurysms of the internal carotid artery with flow diversion
  1. Maxim Mokin1,
  2. Angel Chinea1,
  3. Christopher T Primiani1,
  4. Zeguang Ren1,
  5. Peter Kan2,
  6. Visish M Srinivasan2,
  7. Ricardo Hanel3,
  8. Pedro Aguilar-Salinas3,
  9. Aquilla S Turk4,
  10. Raymond D Turner4,
  11. M Imran Chaudry4,
  12. Andrew J Ringer5,
  13. Babu G Welch6,
  14. Vitor Mendes Pereira7,
  15. Leonardo Renieri7,
  16. Mariangela Piano8,
  17. Lucas Elijovich9,
  18. Adam S Arthur9,
  19. Ahmed Cheema9,
  20. Demetrius Klee Lopes10,
  21. Ahmed Saied10,
  22. Blaise W Baxter11,
  23. Harris Hawk11,
  24. Ajit S Puri12,
  25. Ajay K Wakhloo12,
  26. Hussain Shallwani13,
  27. Elad I Levy13,
  28. Adnan H Siddiqui13,
  29. Guilherme Dabus14,
  30. Italo Linfante14
  1. 1Department of Neurosurgery, University of South Florida, Tampa, Florida, USA
  2. 2Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA
  3. 3Department of Lyerly Neurosurgery, Baptist Medical Center Jacksonville, Jacksonville, Florida, USA
  4. 4Medical University of South Carolina, Charleston, South Carolina, USA
  5. 5Department of Neurosurgery, Mayfield Clinic, University of Cincinnati, Cincinnati, Ohio, USA
  6. 6Department of Neurological Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA
  7. 7Division of Neuroradiology, University Health Network - Toronto Western Hospital, Toronto, Ontario, Canada
  8. 8Department of Neuroradiology, Grande Ospedale Metropolitano Niguarda, Milano, Italy
  9. 9Semmes-Murphey Neurologic and Spine Institute, Semmes-Murphey Clinic, Memphis, Tennessee, USA
  10. 10Department of Neurological Surgery, Rush University Medical Center, Chicago, Illinois, USA
  11. 11Department of Radiology, University of Tennessee, Erlanger Hospital, Knoxville, Tennessee, USA
  12. 12Department of Radiology, University of Massachusetts, Worcester, Massachusetts, USA
  13. 13Department of Neurosurgery, University at Buffalo, State University of New York, Buffalo, New York, USA
  14. 14Miami Cardiac and Vascular Institute, Baptist Hospital, Miami, Florida, USA
  1. Correspondence to Dr Maxim Mokin, Department of Neurosurgery, University of South Florida, Tampa, FL 33620, USA; mokin{at}health.usf.edu

Abstract

Background Blood blister aneurysms (BBA) are a rare subset of intracranial aneurysms that represent a therapeutic challenge from both a surgical and endovascular perspective.

Objective To report multicenter experience with flow diversion exclusively for BBA, located at non-branching segments along the anteromedial wall of the supraclinoidal internal carotid artery (ICA).

Methods Consecutive cases of BBA located at non-branching segments along the anteromedial wall of the supraclinoidal ICA treated with flow diversion were included in the final analysis.

Results 49 patients with 51 BBA of the ICA treated with devices to achieve the flow diversion effect were identified. 43 patients with 45 BBA of the ICA were treated with the pipeline embolization device and were included in the final analysis. Angiographic follow-up data were available for 30 patients (32 aneurysms in total); 87.5% of aneurysms (28/32) showed complete obliteration, 9.4% (3/32) showed reduced filling, and 3.1% (1/32) persistent filling. There was no difference between the size of aneurysm (≤2 mm vs >2 mm) or the use of adjunct coiling and complete occlusion of the aneurysm on follow-up (P=0.354 and P=0.865, respectively). Clinical follow-up data were available for 38 of 43 patients. 68% of patients (26/38) had a good clinical outcome (modified Rankin scale score of 0–2) at 3 months. There were 7 (16%) immediate procedural and 2 (5%) delayed complications, with 1 case of fatal delayed re-rupture after the initial treatment.

Conclusions Our data support the use of a flow diversion technique as a safe and effective therapeutic modality for BBA of the supraclinoid ICA.

  • aneurysm
  • flow diverter
  • subarachnoid

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Introduction

Blood blister aneurysms (BBA) are a rare subset of intracranial aneurysms that represent a therapeutic challenge from both a surgical and endovascular perspective. These vascular lesions are classically described arising at non-branching, curved segments along the anteromedial wall of the supraclinoidal internal carotid artery (ICA), morphologically consisting of a broad base with a thin fibrous wall comprised of tunica adventitia.1–6 The pathophysiology of how BBA form is unclear but their clinical nature suggests these aneurysms arise due to hemodynamic stress causing a focal injury on the vascular lumen.1–3 7

Blister aneurysms represent only 0.3–1% of all intracranial aneurysms, 0.9%–6.5% of ICA aneurysms, and constitute about 1.0% of all ruptured aneurysms.1 2 4–9 The traditional approach to the neurosurgical treatment of BBA includes clip reconstruction with or without aneurysm wrapping, reserving arterial bypass as a rescue or last resort option in select cases.2 5 7 9 Even in experienced hands, BBA represent a surgical dilemma, where intraoperative rupture rates have been reported to be up to 50% compared with the 7% seen with saccular aneurysms.5 8 9 This has promoted research into considering advancing neurovascular approaches for the treatment of this distinct pathology.

Endovascular interventions were initially faced with skepticism, citing the risk of incomplete aneurysm occlusion in the acute period, as well as the risk of rupture or rebleeding reported from traditional coiling techniques.4 5 There was also a concern over the need for continued antiplatelet therapy with the use of stents or flow diverters, as this patient population may require further invasive procedures and carry an increased intracranial hemorrhage risk.5 9–11

Flow diversion has become a promising option for the treatment of BBA, with studies showing high long term occlusion and low complication rates.8 10 12–14 Unfortunately, the studies describing the treatment of BBA of the ICA with flow diversion frequently include cases of blister aneurysms at other anatomical locations, as well as aneurysms of different morphology, such as dissecting or fusiform aneurysms. This has limited our understanding of the safety and limitations of flow diversion technology when specifically applied for the treatment of ‘traditional’ ICA blister aneurysms.

In this study, we reviewed multicenter experience with flow diversion exclusively for BBA located at non-branching segments along the anteromedial wall of the supraclinoidal ICA.

Methods

The study was approved by the local institutional review board at each participating center for retrospective data collection and review. Consecutive cases of BBA located at non-branching segments along the anteromedial wall of the supraclinoidal ICA treated with flow diversion between January 2011and April 2017 were included in the study. Treatment of BBA was based on each operator preference, including timing of the procedure, choice and number of devices, administration and dose of antiplatelet agents, and postprocedure care.

Baseline and postprocedural imaging studies, including CT, MRI, and DSA, were reviewed by local investigators at each participating site and were not adjudicated by a central core laboratory. Statistical analyzes included χ2, one way ANOVA, and multivariate analysis, and were performed using SPSS (IBM SPSS Statistics for Windows, v.24, IBM Corp, Armonk, New York, USA).

Using the PubMed database and search terms ‘flow diversion’, ‘pipeline embolization device’, ‘blister aneurysm’, ‘blood blister aneurysm’, ‘ruptured’, and ‘internal carotid artery’, we identified studies published between January 2011 and April 2017 that specifically reported radiographic and clinical outcomes, and complications in cases of ICA BBA aneurysms treated with flow diversion. We excluded cases of BBA at other locations or aneurysms that were dissecting or fusiform in morphology.

Results

There were a total of 49 patients with 51 BBA of the ICA treated with devices to achieve the flow diversion effect from 14 participating centers. Of those, the vast majority (88%, 43 patients with 45 BBA of the ICA) were treated with the pipeline embolization device (PED; Medtronic, Irvine, California, USA), and were included in the final analysis.

Of the 43 cases treated with the PED, two patients had two separate tandem BBA of the ICA treated in the same session. Mean age was 52.8±13.9 years and 67% (29/43) were women. Baseline clinical and imaging characteristics of these 43 cases treated with the PED are shown in table 1. Median aneurysm size was 2.4 mm. Median duration from subarachnoid hemorrhage (SAH) onset to treatment was 1 day. Two patients required two PEDs during the procedure; all other cases required a single PED.

Table 1

Baseline clinical and radiographic data of 43 patients with blood blister aneurysms of the internal carotid artery treated with a pipeline embolization device

Forty-two of 43 patients were maintained on dual antiplatelet therapy (DAPT) after placement of flow diversion devices. In one case, intracerebral hemorrhage was discovered immediately after the procedure, precluding the use of antiplatelet therapy. The description and management of intra- and periprocedural complications in the firs 24 hours are summarized in table 2. Acute intraprocedural in-stent thrombosis occurred in four cases and was the most common complication out of seven total early complications of BBA embolization with the PED (table 2). All cause inhospital mortality was 19% (8/43 patients). A combination of aspirin and clopidogrel was the most common DAPT regimen, which was used in 86% (37/43) of cases. Other choices of DAPT included the use of prasugrel or ticagrelor instead of clopidogrel. Intraprocedural IIb/IIIa inhibitor agents were administered in 37% (16/43) of cases. Immediate change in contrast opacification at the end of the procedure described as partial filling or no residual aneurysm filling was reported in 42% (19/45) and 27% (12/45) of treated blister aneurysms, respectively.

Table 2

Complications associated with treatment of blood blister aneurysms using the pipeline embolization device

Angiographic follow-up data were available for 30 patients (32 BBA in total) and were performed, on average, 4 months after the treatment. A total of 88% of aneurysms (28/32) showed complete obliteration, 9% (3/32) showed reduced filling, and 3% (1/32) showed no change in contrast filling during angiographic follow-up. There was one case of moderate in-stent stenosis and one case of in-stent thrombosis with total occlusion recognized on follow-up angiography; both patients remained asymptomatic.

Clinical 3 month follow-up data were available for 38 of 43 patients, and 68% of patients (26/38) had a good clinical outcome (modified Rankin Scale (mRS) score of 0–2) at 3 months. The description and management of remote complications related to the use of the PED and DAPT are summarized in table 2.

We found that 60% (27/45) of aneurysms were >2 mm. There was no difference between size of aneurysm (≤2 mm vs >2 mm) and complete occlusion of the aneurysm on follow-up (P=0.354). The use of adjunct coiling did not affect aneurysm occlusion on the follow-up study (P=0.865). Furthermore, there was no association between aneurysm filling immediately after placement of a flow diverter at the end of procedure versus complete occlusion at follow-up (P=0.548). Low grade SAH (Hunt Hess I–III) and a lower Fisher grade were associated with better outcomes, determined by 3 month mRS scores ≤2 (P<0.001 and P=0.047, respectively).

Radiographic and clinical data of the six patients with BBA treated with devices other than the PED to achieve the flow diversion effect are summarized in table 3.

Table 3

Radiographic and clinical data of 6 patients with blood blister aneurysms treated with devices other than the pipeline embolization device to achieve the flow diversion effect

Discussion

Endovascular interventions utilizing flow diversion are becoming widely accepted for the treatment of BBA. A variety of devices and techniques have been described in the literature, although cases are scarce given the rarity of BBA. Given this, cases of BBA of the ICA are often combined with BBA at other anatomical locations, or include ICA lesions with a different morphology, limiting our ability to understand the safety and efficacy of flow diversion when applied to ICA BBA specifically. This study evaluated 49 cases presenting with BBA at non-branching sections of the ICA treated with a multitude of flow diverting devices. Because of a disproportionally high number of BBA treated with PED, in order to provide the reader with a more practical data set, we limited our analysis mainly to the 43 cases treated with the PED. Also, it is presently debatable what devices should be considered ‘true’ flow diverters, and therefore, focusing our attention on the use of the PED alone helped us avoid such uncertainty. Computational fluid dynamic analysis suggests that different flow diverters or overlapping stents vary in their hemodynamic effects on cerebral aneurysms, such as changes in wall shear stress and velocity.15 This is the largest multicenter series published to date describing this unique vascular pathology, and our results support the use of flow diversion in general, and the PED specifically, as a safe and effective treatment for this group of patients.

At present, the PED is the most commonly studied flow diverting stent for the treatment of BBA, as shown by ours and other studies.8 10 16–20 The use of flow diversion technology has raised concerns regarding potential complications intrinsic to its design. One such issue is the incomplete or delayed occlusion rates encountered with the use of flow diversion, which is less commonly seen with traditional coiling. In particular, several authors challenge the use of the PED in the setting of acute SAH, citing an increased risk of rebleeding, growth, and downstream neurologic decline resulting from an unsecured aneurysm.4 5 9 The literature does not support this statement, as recent studies have not shown an increased re-hemorrhage risk with the PED, even with confirmed residual aneurysm.16 18–21 Additionally, complete occlusion is usually observed in 80–90% of cases on follow-up angiography.6 8 10 11 17 20 Some authors have even demonstrated complete occlusion of BBA immediately following PED placement.6 17 19 Such a low incidence of rebleeding in the immediate period can be explained by the reduction of jet inflow of blood and hemodynamic sheering stress on the aneurysmal wall, therefore addressing the factors that predispose to rupture/rebleeding.11 22

Our results concur with those previously reported, with 88% of aneurysms showing complete obliteration and 9% of aneurysms with reduced filling on follow-up angiography. Interestingly, we found that the use of adjunct coiling did not affect the rate of complete occlusion on follow-up angiography. Another important finding in our series is that the lack of immediate changes in contrast filling within the aneurysm after placement of a flow diverter intraprocedurally (which is often witnessed angiographically when larger aneurysms are treated with flow diverters) was not predictive of incomplete aneurysm occlusion on follow-up. It would also be important to further study whether there are differences in blood pressure goals for patients with aneurysm dome showing persistent filling at the end of embolization, which may be perceived to be ‘unsecured’. We did not have the data available to investigate if such a correlation exists. There is a possibility that differences in blood pressure parameters for such patients may influence their hospitalization course.

The requirement for DAPT in the setting of acute SAH is also of concern, given that these patients may require invasive procedures, such as ventriculostomies, ventriculoperitoneal shunts, or tracheostomies in the acute and subacute period.4 5 9 11 In the largest systematic review regarding endovascular treatment for ruptured blister-like aneurysms, Rouchard et al reported a 17% incidence of procedural complications, 11.5% perioperative stroke, and a 7.6% perioperative intracerebral hemorrhage  for a combined 12.6% and 8.7% periprocedural morbidity and mortality, respectively, with the use of flow diversion.8 Despite these findings, long term neurologic outcomes were superior to other endovascular treatments (such as coiling or stent assisted coiling) with 80% of patients having a mRS score of ≤2.8 In a comprehensive meta-analysis of the literature, morbidity and mortality associated with BBA was lower than with surgical treatment, even in the presence of DAPT.6 More recently, studies evaluating the use of flow diversion for treatment of ruptured aneurysms rarely exhibit ventriculostomy related tract hemorrhage, and when observed patients tend to remain asymptomatic.10 12–14 16 18–20

Evaluating previously published individual case series utilizing flow diversion for the treatment of BBA of the ICA revealed an overall low incidence of clinically significant complications (table 4).6 10 11 14 16 17 19 21 Similarly, most periprocedural complications in our series were effectively managed without long term effects, with 68% (26/38) of patients maintaining a good neurologic outcome at clinical follow-up. We found one case each of asymptomatic in-stent stenosis and in-stent thrombosis discovered on follow-up angiography.

Table 4

Studies of internal carotid artery blood blister aneurysms treated with flow diversion

Limitations of our study include its retrospective nature, which is subject to the accuracy of case reporting. We also had different treatment protocols at the participating institutions affecting the generalizability of the results. The follow-up period is also shorter than some of the studies in the literature and limited by patients lost to follow-up throughout the study period. Angiographic follow-up data were not available in 30% of patients, and imaging studies were not adjudicated by a central core laboratory. Lastly, this dataset mainly included patients that underwent treatment of BBA with the use of the PED. Further studies with large numbers of patients treated with other types of flow diversion devices are needed.

Conclusion

This multicenter study includes the largest single series of patient treated with the PED for BBA of the ICA. Our data support this endovascular technique as a safe and effective therapeutic modality for this pathology.

References

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Footnotes

  • Contributors MM and IL: study concept and design. MM and AC: wrote the manuscript. MM and CTP: statistical analysis. All authors participated in data collection and analysis, edited the manuscript, and approved the final version.

  • Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests ASA: consultant for Covidien, Johnson and Johnson, Siemens, Stryker, and Terumo; grants from Siemens and Terumo. BWB: personal fees from Penumbra Inc, Stryker, Medtronic, Route 92 Medical, and Pulsar. MIC: consultant for Penumbra, Medtronic, Microvention, Codman, Pulsar Vascular, Q’Apel, Rebound Medical, and Blockade Medical. GD: consultant for Proctor; speakers bureau for Medtronic and Microvention; shareholder in Medina Medical, InNeuroCo, and Stryker/Surpass. LE: consultant for Stryker Neurovascular, Microvention, and Codman Neurovascular. RH: consultant for Covidien, Stryker, Codman, and MicroVention. PK: consultant for Stryker Neurovascular, Covidien, and MicroVention. EIL: shareholder/ownership interests in Intratech Medical Ltd, Blockade Medical LLC, and Medina Medical; principal investigator in Covidien US SWIFT PRIME Trials; honoraria for training and lecturing from Covidien; consultant for Pulsar, Medina Medical, and Blockade Medical; other financial support from Abbott for carotid training for physicians. IL: consultant and speaker bureau for Covidien, Codman, and Stryker. DKL: consultant for Covidien and Stryker; shareholder/ownership in Penumbra and Blockade Medical; advisory board for Siemens; principal investigator for Liberty Trial (Penumbra). VMP: consultant for Medtronic, Stryker, Penumbra, and BALT; research grant from Philips. MM: consultant for Toshiba (Canon) Medical. ASP: consultant for Medtronic Neurovascular and Stryker Neurovascular; research grants from Medtronic Neurovascular and Stryker Neurovascular. AJR: consultant for Stryker, MicroVention, and Covidien/ev3. AHS: grants from National Institutes of Health/NINDS/NIBIB, University at Buffalo–none related to present study; financial interests in Hotspur, Intratech Medical, StimSox, Valor Medical, Blockade Medical, and Lazarus Effect; consultant for Codman & Shurtleff Inc, Concentric Medical, ev3/Covidien Vascular Therapies, GuidePoint Global Consulting, Penumbra, Stryker, Pulsar Vascular, MicroVention, Lazarus Effect, and Blockade Medical; speakers bureau for Codman & Shurtleff Inc; National Steering Committee for Penumbra Inc 3D Separator Trial, Covidien SWIFT PRIME trial, and MicroVention FRED trial; advisory boards for Codman & Shurtleff and Covidien Neurovascular; honoraria from Abbott Vascular, Codman & Shurtleff, and Penumbra Inc. AST: consultant for Stryker, Codman, Penumbra, and Microvention; research grants (not related to the present study) from Stryker, Codman, Micorvention, Penumbra, and Covidien; financial interests in Medina Medical, Lazarus Effect, Pulsar Vascular, and Blockade Medical. RDT: consultant for Penumbra, Medtronic, Microvention, Codman, Pulsar Vascular, Q’Apel, Rebound Medical, and Blockade Medical. AKW: consultant for Stryker Neurovascular; research grants from Philips Healthcare, and Wyss Institute; speaker for Harvard Postgraduate Course and Miami Cardiovascular Institute. BGW: consultant for Stryker and Medtronic.

  • Ethics approval The study was approved by the institutional review board at each participating institution.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement All data were presented in this study.