Flow-diverter stents in the endovascular treatment of remnants in previously clipped ruptured aneurysms: a feasibility study

Abstract

Background

The rate of intracranial aneurysm remnants/recurrences after microsurgical clipping varies widely. The optimal management for these patients remains a matter of debate. Repeat surgery in particular bears a high risk of periprocedural complications due to anatomical distortion from prior procedures. This study aims to evaluate the risk–benefit profile of flow-diverter stents in these patients.

Methods

The patient database of our neurovascular centre was queried to identify patients with clipped aneurysms who subsequently underwent endovascular treatment with intraluminal flow-diverter stents. The outcome analysis consisted of an assessment of clinical parameters (modified Rankin scale) and the post-interventional angiographic occlusion status (according to the Raymond–Roy occlusion classification).

Results

Six patients underwent endovascular treatment with flow-diverter stents of recurrent aneurysms after clipping. Treatment was necessary in two patients due to progressive neurological deficits, and due to angiographic proof of an increasing aneurysm size in the other four patients. Median aneurysm size was 0.45 cm. All patients had a prior history of subarachnoid haemorrhage. The time from primary clipping to recurrence was 10.6 years. Complete radiological aneurysm occlusion was feasible in five out of six cases. Two patients who had experienced pre-interventional neurological deficits showed a complete remission of symptoms on last follow-up. No periprocedural morbidity or mortality was recorded and no patient required retreatment within the median follow-up.

Conclusion

This case series suggests that endovascular treatment with flow-diverter stents of aneurysm remnants after previous microsurgical clipping is a feasible treatment concept with a low-risk profile, which might prevent the treatment burden and risks of repeat surgery.

Introduction

The rate of intracranial aneurysm remnants/recurrences after microsurgical clipping varies between 2% and 42%.¹ This relatively large range is mainly due to: (a) a lack of standardised follow-up in surgical series (in comparison to coiled aneurysms that are predominantly controlled by digital subtraction angiography; DSA); and (b) unclear definition of recurrence and/or (micro)-residual remnants.² Recurrences/remnants can become symptomatic or even result in subarachnoid haemorrhage (SAH) in at least 2% of cases and constitute a therapeutic challenge.¹ Compared to the primary situation, standardised treatment algorithms are missing and most treatment decisions are individualised. The relatively scarce retrospective literature on this topic focusses on three major salvage treatment options: re-surgery, coiling and flow diversion with flow-diverter stents (FDSs).^3–5 Re-surgery comprises techniques such as clipping only, clipping with protective bypass and trapping with bypass reconstruction.⁶ Still, any sort of re-surgery bears a high risk of periprocedural complications due to scarring and anatomical distortion. Severe adhesions may hamper crucial surgical steps.⁷ The few available data on coiling in the salvage situation indicate that this option is almost exclusively suitable for aneurysms with clip-induced narrow-neck aneurysms. Thus this technique is limited to a specific subgroup only.⁵ The third – rarely used – option is FDSs. These devices promote flow stasis in the aneurysm through a woven design that hampers blood outflow, subsequently leading to aneurysm obliteration. During the past decade FDSs have established their role in the endovascular treatment of primary wide-neck, fusiform, large or giant aneurysms.^8–10 However, there is little experience with the use of FDSs in previously clipped aneurysms. This is in contrast to a considerable amount of data focusing on previously coiled aneurysms, in which the technique has been shown to be effective and safe in selected patients.^11–13

This feasibility study aims to evaluate the risk–benefit profile of FDSs as an endovascular treatment option for recurrent aneurysms in patients who had previously undergone clipping after aneurysmal SAH. Special focus was set on the radiological occlusion status, the clinical status, treatment-associated morbidity, treatment burden as well as possible advantages/drawbacks of the treatment.

Methods

Patient population

The institutional database of our neurovascular centre of the Paracelsus Medical University of Salzburg was retrospectively queried for patients undergoing salvage interventional treatment between June 2010 and November 2016. Six patients with previously clipped ruptured aneurysms with proof of radiological and/or neurological deterioration and subsequent treatment with FDSs were identified. Both clinical and radiological data were determined: the clinical status and treatment-associated morbidity were investigated by neurological follow-up including the assessment of the modified Rankin scale (mRS). The extent of angiographic occlusion was determined according to the Raymond–Roy occlusion classification (RROC).^14,15 Written informed consent for the conducted procedures was obtained from all patients.

FDS technique

The technique of FDS has previously been described in detail.¹³ In brief, all patients underwent a platelet inhibition test and subsequently received dual antiplatelet therapy (aspirin and clopidogrel) preoperatively. Heparinised saline (1000 units of heparin per litre of saline) was administered during the embolisation. A triaxial system consisting of a 6-French macrocatheter and Phenom or Marksman (Medtronic) microcatheters were used in all procedures. The position of the FDS was documented by fluoroscopy in anterior–posterior, lateral and rotation views both during and after the intervention as well as three-dimensional rotational DSA. Post-interventionally, patients were discharged after 4 days. Dual antiplatelet therapy was given for at least 6 months.

Clinical and radiological follow-up

Clinical parameters were determined using patients' electronic medical records and paper charts. Treatment decisions were agreed on by the neurovascular board. Neurological status and mRS were assessed pre-interventionally and at discharge. Further clinical follow-up evaluations were conducted at 3–6-month intervals, depending on the individual patient's clinical status. Radiological follow-up was routinely performed by DSA and in selected cases completed by magnetic resonance imaging scans. Radiological outcome was classified with the angiographic occlusion classification proposed by Raymond and Roy (RROC). In brief, the classification scheme subdivides aneurysmal remnants into three classes: class I: complete obliteration; class II: residual neck; class III: residual aneurysmal sac.¹⁴

Treatment-associated symptomatic effects including peri-interventional morbidity or neurological deficits were recorded for all patients. Also, the average length of hospitalisation including the stay in the intensive care unit was assessed.

Results

Patient and aneurysm characteristics

The basic demographic parameters are summarised in Table 1. The median age of the identified six patients (two men and four women) was 51.3 years (range 28–62 years). The median time from primary clipping to aneurysm recurrence was 10.6 years (range 1–30 years). All patients had a history of SAH leading to primary treatment. One patient presented with vertigo and headache when the aneurysm was initially diagnosed. At recurrence two out of six patients were symptomatic, with impaired vision and hemiparesis, respectively. The other four patients had radiological proof of aneurysm recurrence/remnant with no associated neurological dysfunction. Aneurysm recurrence/remnant localisation is shown in Table 1. The median size was 4.5 mm³ (range 1.7–15 mm³). As to lateralisation, five recurrences/remnants were found on the left, one in the right hemisphere.

Table 1.

Patient characteristics.

	Total
Number of patients	6
Age (years) median (range)	51.3 (28–62)
Gender male/female	2/4
History of SAH	6/6
Pre-interventional FND	6/6
Lateralisation left/right	5/1
Aneurysm location
MCA	2
ACom	2
ICA bifurcation	1
PCom	1

SAH: subarachnoid haemorrhage; FND: focal neurological deficit; MCA: middle cerebral artery; ACom: anterior communicating artery; ICA: left internal carotid artery; PCom: posterior communicating artery.

Clinical and radiological outcome data

All of the aneurysms had postoperative angiographic follow-up and showed complete occlusion in five out of six patients. The one patient with a class III residual aneurysmatic sac was the patient who had the largest aneurysm of 15 mm³ size. Both patients who had initially presented with symptoms showed complete remission of their neurological deficits on last follow-up: last recorded mRS was 0 in four patients and 1 in two patients. A detailed overview of the aneurysm characteristics is provided in Table 2. There was no periprocedural morbidity nor mortality and no need for retreatment within the median follow up of 8 months.

Table 2.

Aneurysm configuration characteristics.

Before FDS					After FDS
Patient	Neck (mm)	Width	Depth	Height	RROC
1	3.5	8.6	4	12.4	I
2	3	3.6	4.2	2.9	I
3	3.3	5.8	3.6	3.4	I
4	2.2	4	3.8	2.6	I
5	4.4	11.6	13.3	16.6	III
6	1.6	2	1.5	2	I

FDS: flow-diverter stent; RROC: Raymond–Roy occlusion classification.

Presentation of a representative case

A 62-year-old female patient had undergone microsurgical clipping of a wide-neck posterior communicating artery (PCom) aneurysm 20 years before presentation. The patient had experienced a chronic tension headache but was otherwise asymptomatic, the follow-up DSA showed evidence of an aneurysm recurrence/remnant in the base of the PCom measuring 3 × 5 mm (Figure 1). For the FDS procedure, the guide catheter was advanced from the left internal carotid artery and the FDS could be safely placed onto the PCom aneurysm (Figure 2). Correct positioning was verified in anterior–posterior and lateral views as well as in rotation. The post-interventional course was uneventful and the patient was discharged after 4 days. Follow-up DSA including three-dimensional rotational DSA after 6 and after 12 months showed complete occlusion of the aneurysm (angiograph after 6 months, see Figure 3).

Figure 1.

Lateral views of the internal carotid angiograms: (a) base image; (b) detailed image shows the presence of a post-clipping aneurysm resting on the posterior communicating artery ((b) arrow).

Figure 2.

Lateral views of the left internal carotid angiograms. Flow-diverter stent (FDS) placement in the arterial phase delineates the posterior communicating artery aneurysm (a) with evidence of isolated filling demonstrating FDS-induced tubular flow ((b) arrow).

Figure 3.

Three-dimensional rotational digital subtraction angiography before (a) and after (b) 6 months of flow-diverter stent placement showing complete aneurysm occlusion ((a and b) arrows).

Discussion

The remnant/recurrence rate of previously clipped aneurysms is likely to be underestimated.³ Moreover, there is no agreement on the optimal treatment due to lack of large-scale evidence. This renders the issue of the optimal treatment of recurrent aneurysms a main topic of interest for the neurovascular community. From a surgical perspective, re-operation is difficult and often not feasible due to scarring and distorted anatomy.² The structure of the previously applied clip and its relation to the new aneurysm is essential for a successful occlusion. Any sort of manipulation, however, is often complicated by (hypertrophic) scar formation rendering the procedure technically not practicable.⁷ Reports in the literature identified the risk of cerebral infarction and seizures being 16% after re-surgery in these aneurysms; oftentimes, postsurgical occlusion rates are not documented.^3,6,7,16

As for coiling, only very selected previously clipped aneurysms appear to be suitable for this treatment. In one of the largest series, El Beltagy and colleagues recommend avoiding large wide-neck aneurysms or any aneurysm associated with incorporated vessels.³ In all of our patients, we found a wide base configuration of the aneurysm remnants; therefore, intravascular devices or simple coiling were not deemed to be feasible. Also, in the literature, a rate of up to 21% coil recanalisation/coil compaction as well as procedure-related complications (i.e. aneurysm perforation, rupture, distal thromboembolism) and post-procedural complications such as transient ischaemic attack, stroke or distal haemorrhage had been reported.^2,5,17–19 In these cases, complete occlusion was achieved in 42.9–79% of cases; residual neck was identified in 21–57.1% of cases.^2,5,17

Here, we present a single-centre series of previously clipped aneurysms treated by FDS focussing on the neurological and radiomorphological outcome. In the past, this treatment option has been associated with in-stent stenosis or post-interventional chronic headache during post-interventional follow-up.^5,20 With regard to radiological follow-up, our data are in line with the literature in which follow-up DSA demonstrated complete aneurysmal occlusion in most cases.^9,13,20–22 Regarding a potentially problematic FDS visualisation: in the present study a diagnostic angiography with a rotational technique was deployed. Due to a dual volume acquisition mode, a perfect clip subtraction could be achieved. This subsequently led to excellent FDS visualisation and negligible clip-induced artefacts. In one of our patients a remnant portion of the aneurysmatic sac was seen (pre-interventional aneurysm size: 15 mm). This finding might indicate that FDS placement is especially suitable for selected patients with small-sized aneurysm recurrences.

One of the most common problems with recurrent aneurysm treatment following surgical clipping is in-stent restenosis and needs to be addressed. This complication is typically seen within 6 months after stenting. The problem seems to arise from neointimal hyperplasia in approximately 8% of cases leading to documented mortality rates ranging from 3% to 5%.²³ Despite neointimal hyperplasia, the size of the stent itself might contribute to the rate of in-stent restenosis because an oversized stent might increase intramural stress leading to chronic stimulation of smooth muscle proliferation and inflammatory processes. There is no consensus regarding systemic medical treatment. In our patient series a new generation of individual size-adjusted FDSs (Flex Shield) was exclusively utilised and we observed no relevant in-stent stenosis during follow-up. It may well be that these new devices are associated with an overall lower risk of in-stent stenosis. Nonetheless, definite conclusions regarding this issue may only be drawn with caution from our dataset due to the small sample size and limited follow-up period. Obviously, a larger study population is generally necessary to define possible size thresholds and potentially favourable configuration characteristics of previously clipped aneurysms.

The question of having to treat patients with a history of SAH with FDSs resulting in antiplatelet medication needs discussion: antiplatelet medication is a known risk factor for haemorrhagic complications especially in early scenarios after SAH with/without intracerebral haemorrhage. The median latency between clipping after SAH and FDS placement was 18 years in our series. As no haemorrhagic event was registered in our series, it might be discussed that these events are less likely to occur at a later stage of the disease. Still, pondering the risks associated with aggressive antiplatelet treatment always has to be kept in mind in FDS treatment.

Finally, a further aspect is the patient perception of treatment burden. Its impact is critical, as all these patients have undergone extensive hospitalisation at primary presentation due to SAH. An endovascular approach with FDS might help to minimise treatment burden and enhance quality of life providing a durable and safe solution customised to individual patterns.

Conclusion

The treatment of previously clipped aneurysms represents an unmet challenge for the neurovascular community. In our feasibility study, the endovascular treatment with FDS has proved to be effective and safe even in complex configurated recurrent aneurysms. The favourable characteristics of this technique might prevent the treatment burden of repeat surgery.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. For this type of study formal consent is not required.

Declaration of conflicting interests

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: all authors certify that they have no affiliations with or involvement in any organisation or entity with any financial interests (such as honoraria, educational grants, participation in speakers’ bureaux, membership, employment, consultancies, stock ownership, or other equity interest and expert testimony or patent‐licensing arrangements), or non‐financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this article was received for this research.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.