Unruptured giant intracavernous aneurysms untolerate internal carotid artery occlusion test: Untreated and treated with flow-diversion

Abstract

Background and objective

Giant intracavernous aneurysms (GICAs) are located in extradural space; their clinical manifestation and treatment are different from other intradural aneurysms. This study reports clinical outcomes of GICAs untolerate internal carotid artery occlusion tests.

Methods

Between January 2012 and September 2017, 14 consecutive cases of GICAs untolerated internal carotid artery occlusion test were retrospectively reviewed. A total of nine patients were not treated and five patients were treated using a Pipeline Embolization Device.

Results

Of the 14 patients, 12 had compression symptoms and 2 were incidental. In nine untreated patients, during 34 months' (range, 7–64 months) follow-up, four worsened to headaches or ablepsia (more than 34 months). One patient, who presented with ophthalmoplegia and diplopia, showed spontaneous resolution of symptoms at 32-month follow-up. Symptoms in four patients remained unchanged during less than 36-month follow-up period. In five (100%, 95% confidence interval 57% to 100%) treated patients, symptoms recovered completely during 11 months' follow-up after transient worsening of mass compression.

Conclusions

GICAs frequently result in intractable cranial neuropathy requiring treatment. The Pipeline Embolization Device is an effective option for these complex aneurysms in selective cases.

Introduction

Giant intracavernous aneurysm (GICA) refers to those lesions larger than 2.5 cm and derived from a carotid cavernous segment.¹ Most GICAs are considered benign lesions referring to intradural giant aneurysms and have a natural history with a low risk of life-threatening complications. GICA is usually recognized because of mass effect.¹ The main difference between smaller and giant cavernous aneurysms is the optic nerve compression.² Many reports on endovascular treatment of intracavernous aneurysms by balloon occlusion or coiling have now been published.³ Flow diverters have added a new dimension and represent a paradigm shift in the treatment of intracranial aneurysms.⁴ The Pipeline Embolization Device (PED; Medtronic Neurovascular, Irvine, California, USA) has become a routine first-line treatment option for large and giant internal carotid artery aneuryms.⁵ The systematic review reported a neurologic morbidity and mortality rate of 11.8%, where most of the adverse events were thromboembolic and hemorrhagic complications.⁶ A second-generation PED with a redesigned delivery system, the Pipeline Flex Embolization Device, received CE mark and FDA approvals in 2014 and 2015, respectively.⁷ This study reports clinical outcomes of untreated GICAs and GICAs treated with Pipeline and Pipeline Flex flow-diversions.

Materials and methods

Between January 2011 and September 2016, 14 consecutive cases of unruptured GICAs that failed a balloon test occlusion (BTO) were retrospectively reviewed. Nine patients were not treated and five patients were treated using a PED. The 14 patients included 3 men and 11 women who ranged in age from 19 to 74 years (mean age 54 years). No patient had a history of head trauma. Diagnosis was based on clinical manifestations and findings of radiological examinations including computed tomography scanning, magnetic resonance imaging (MRI) and cerebral angiography in all patients. All patients underwent clinical follow-up examinations.

Pipeline Embolization Device procedure

Patients were prepared with double antiaggregation (clopidogrel 75 mg and aspirin 100 mg) 5 days prior to the procedure. After general anesthesia, an 8F femoral sheath was placed and a 6F-long sheath (COOK, California, USA) was selectively placed into the corresponding common carotid artery. A distal flexible catheter Navien 6F (Covidien Neurovascular, Irvine, California, USA) was placed selectively into the internal carotid artery (ICA) at the level of the petrous segment. Then, a Marksman microcatheter (Covidien, Irvine, California, USA) was navigated distal to the GICA at the level of the middle cerebral artery through a 14-inch guidewire. Then an Echelon10 microcatheter (Covidien, Irvine, California, USA) was navigated into the aneurysm sac for coiling. For all cases, we planned one stent layer with associated coiling. Clinical and imaging (magnetic resonance angiography and angiography) follow-up was planned at 6 months.

Results

Untreated patients

Among nine patients, eight (88.9%) presented with cranial nerve symptoms caused by compression (Table 1). The other one (11.1%) patient was diagnosed incidentally. One patient (11.1%) experienced transient ophthalmoplegia and diplopia but recovered fully without any neurological deficits at 32-month follow-up. Four of these patients (44.4%) had no clinical changes in the 36-month follow-up period. Two patients (22.2%) deteriorated more than 33 months after initial presentation, resulting in complete blindness of the involved eye. The remaining two patients (22.2%), who presented with diplopia and ophthalmoplegia, developed new onset of headaches after more than 38 months.

Table 1.

Untreated patients' demographics and outcomes.

Patient	Age (years)	Sex	Maximum diameter (mm)	Presentation	Follow-up (months)	New symptoms at follow-up
1	49	F	26	Ophthalmoplegia, diplopia	64	Headache
2	70	F	29	Diplopia, ophthalmoplegia	38	Headache
3	74	F	26	Ophthalmoplegia, visual blurring	54	Ablepsia
4	70	F	35	Visual blurring	33	Headache, ablepsia
5	19	M	28	Ophthalmoplegia, diplopia	32	Asymptomatic
6	57	F	26	Asymptomatic	33	Asymptomatic
7	38	M	60	Ablepsia, headache	36	NO
8	65	F	31	Headache, diplopia	11	NO
9	54	F	34	Diplopia, visual blurring	7	NO

F: female; M: male; NO: none.

Treated with PED

Five patients were treated with Pipeline and Pipeline Flex (Table 2). Four patients presented with progressive cranial nerve symptoms caused by compression. The other one (20%) patient was found incidentally. Five (100%, 95% confidence interval 57% to 100%) patient experienced transient headache after treatment within 3 months but had recovered fully without any neurological deficits at last follow-up. Control angiograms obtained in four patients at 6 months' follow-up showed complete occlusion of aneurysms.

Table 2.

Flow-diversion treated patients' demographics and outcomes.

Patient	Age (years)/ sex	Maximum diameter (mm)	Symptoms	Treatment	Follow-up (months)	Status at last follow-up
1	70/F	30	Visual blurring	PED	30	Asymptomatic
2	28/M	28	Ophthalmoplegia, diplopia	PED	28	Asymptomatic
3	50/F	30	Asymptomatic	PED	20	Asymptomatic
4	60/F	35	Headache, diplopia	PED	12	Asymptomatic
5	52/F	39	Diplopia, headache	PED Flex	8	Asymptomatic

F: female; M: male; PED: Pipeline Embolization Device

Case illustrations

Case 1

Case 1 was a 38-year-old patient with a 2-year history of headaches, left eye blindness and ophthalmoplegia caused by a GICA (Figure 1). Computed tomography of the head suggested a large mass in the left cavernous parasellar region 60 mm in diameter with sphenoidal sinus and small wing defiguration. Slight calcification was noted in the peripheral portion of the mass. MRI, with or without enhancement, and magnetic resonance angiography of the brain revealed the presence of a giant, partially thrombosed aneurysm with residual flow through a serpiginous lumen within its thrombosed portion. Cerebral angiography demonstrated a partially thrombosed giant aneurysm arising from the left cavernous ICA. The serpiginous lumen filled slowly and supplied blood to two distal left anterior and middle cerebral arteries directly from the terminate aspect of the giant aneurysm. During BTO for ICA occlusion, there was no collateral filling of the occluded side through the circle of Willis. Considering this condition, no endovascular or surgical treatment was given. At 3-year follow-up, this patient did not present any further progressive symptoms.

Figure 1.

(a) Computed tomography scanning demonstrated a well-circumscribed mass lesion. The hyperdense, thrombosed portion of the aneurysm may also be heterogeneous, indicating different stages of hemorrhage and thrombosis. In addition, a thin peripheral rim of calcification may be noted surrounding the aneurysm, indicating the chronic nature of giant serpentine aneurysms. Erosive osseous changes may be noted within the clinoid process, sella turcica, sphenoidal fissure. (b) T2-weighted axial images showed a large thrombosed aneurysm with peripheral edema in the left frontal area and the hypointense flow void associated with the serpiginous vascular lumen. (c) Post-contrast T1-weighted axial image shows intense homogeneous enhancement of the serpiginous vascular lumen and of the peripheral rim of the aneurysm, while the thrombosed portion of the aneurysm is non-enhancing, which has been coined the ‘target sign’. The target sign is pathognomonic for partially thrombosed aneurysms. The intra-aneurysmal vascular channel is often eccentrically located within the aneurysmal mass and takes a wavy, sinusoidal course. (d) Anteroposterior arterial-phase angiograms show the ectatic vascular channel involving the left internal carotid artery and corresponding to the vascular channel identified on magnetic resonance images.

Case 2

Case 2 was a 52-year-old patient with a 6-month history of diplopia and headaches. An MRI of the head showed a 39 mm mass in the left cavernous parasellar region. Cerebral angiography demonstrated a giant aneurysm arising from the left cavernous ICA. The aneurysm measured 39 mm × 37 mm. This aneurysm was treated with a 4.0 mm × 30 mm Pipeline Flex device with an additional two coils of 25 mm×50 cm (Figure 2). No intraprocedural complications occurred. Just 2 days after the procedure the patient's headache worsened. The diplopia and headache resolved at 3 months. At 6 months, she was asymptomatic and follow-up angiogram showed the aneurysm completely occluded.

Figure 2.

(a) Magnetic resonance imaging of the head showed a giant mass in the left cavernous parasellar region. (b) Right carotid artery angiography, frontal review, demonstrated a giant aneurysm arising from the left cavernous internal carotid artery. (c) Fluoroscopic image showing a 4.0 mm × 30 mm Pipeline Embolization Device Flex placed and contrast stagnation in the aneurysm. (d) Right carotid artery angiography, frontal review, after addition of two coils of 25 mm × 50 cm. (e) Right carotid artery angiography at 8-month follow-up, frontal view, showed disappearance of the aneurysm.

Discussion

GICAs occur with clinical symptoms often resulting from a compressive mechanism although seldom, result from a rupture or hemorrhage.¹ Because GICAs are located in extradural space and hard surrounding structures of the cavernous sinus dura, they have a very small risk of subarachnoid hemorrhage.⁸ However, they can grow larger in size, and can present with symptoms of mass effect on cranial nerves, such as ophthalmoplegia and facial pain or numbness. They may also compress the optic nerve, leading to subsequent loss of vision. In our retrospectively reviewed series of 39 consecutive giant intradural aneurysms,⁹ during a 30 month follow-up, 44.4% patients died and 22.2% deteriorated if the giant aneurysm was left untreated.

Treatment before the flow-diversion era

The appropriate treatment of GICAs differs from other types of aneurysms. Regarding open surgical approaches, direct clipping of GICAs is extremely challenging and difficult, given the complex surrounding venous structures and cranial nerves. Several techniques for indirect treatment of GICAs have been reported in previous literature (Table 3).^10–17 Such techniques include ICA occlusion (direct ligation or gradual occlusion using Selverstone clamp), superficial temporal artery-middle cerebral artery bypass with ICA occlusion, trapping, and high-flow bypass with ICA occlusion or trapping. Conversely, endosaccular coiling of giant aneurysms, with or without stent assistance, is not an effective treatment option for giant aneurysms, resulting 23.3% patient death and 6.7% permanent neurological deficits.⁹ From these reviews, it seems that early parent artery occlusion (PAO) treatment may associate with a higher cure rate contrasted to coil embolization.^18–20 Compared with the 25% neurological deterioration rate, PAO is an effective and safe method for the treatment of symptomatic GICAs if BTO can be tolerated. Patients treated with ICA occlusion should be followed because ICA occlusion has been reported to have high risk for de novo aneurysms, typically on anterior communicating artery. Vasconcellos and colleagues reviewed 20 giant cavernous aneurysms during a 19-year period and found 25% spontaneous thrombosis of ICA with 20% regression of deficit.²¹ Therefore, we believe there is a role for conservative management in patients who are not acutely and severely symptomatic and fail BTO.

Table 3.

Giant intracavernous aneurysms in the literature before flow-diversion era.

Authors, year	Age (years)/ sex	Location	Size (mm)	Presentation	Treatment	Outcome
Fodstad et al., 197812	27/F	L ICA	75	Diplopia, partial CN III and VI palsy, hemifacial paresthesias	L ICA ligation, partial resection	Partial L ophthalmoplegia, CN V palsy
Pinto et al., 197915	NA	R ICA	NA	Diplopia	NA	NA
Vlahovitch et al., 198517	32/F	L ICA	NA	NA	Anastomosis, ICA occlusion	NA
Aletich et al., 199510	20/M	R ICA	55	R optic nerve neuropathy	STA-MCA anastomosis, balloon occlusion ICA and ophthalmic artery	Complete thrombosis of aneurysm, neurologically intact
Mawad et al., 199513	NA	R ICA	NA	NA	BTO, detachable balloon occlusion of parent vessel	NA
	NA	L ICA	NA	NA	BTO, detachable balloon occlusion of parent vessel	NA
	NA	R ICA	NA	NA	NA	NA
Otsuka et al., 200114	48/M	R ICA	40	L hemianopsia, L hemiparesis	Endovascular coil deployment within aneurysm lumen	L hemianopsia, L hemiparesis
Fanning et al., 200311	30/M	L ICA	NA	HA, blurred vision, L CN VI palsy, L eye blindness	BTO, detachable balloon occlusion of parent vessel	Unchanged neurological findings
Prochazka et al., 200716	14/M	L ICA	30	Diplopia, CN III palsy	BTO, detachable coils occlusion of parent vessel	Complete occlusion of aneurysm, neurologically intact

L: left; R: right; ICA: internal carotid artery; NA: not available; CN: cranial nerve; HA: headache; STA-MCA: superficial temporal artery-middle cerebral artery; BTO: balloon test occlusion.

Flow-diversion era

Flow diversion is an established technique for treatment of cerebral aneurysms. A meta-analysis of 29 studies reporting 1524 patients with 1732 aneurysms treated with flow diverters found complete and nearly complete occlusion rates of 84.4%.⁶ This meta-analysis found procedure-related morbidity and mortality rates of 11.8% in the treatment of anterior circulation aneurysms, with higher morbidity and mortality in the treatment of posterior circulation aneurysms. In another of our systematic review studies of PED treatment of GICAs,²² the cumulative mortality rate for PED treatment of giant ICA aneurysms was 10%. Only intradural giant aneurysms are associated with a mortality when compared with intracavernous aneurysms; the morbidity of PED treatment of GICAs is 14.3% without any mortality. There is also a 10% mortality in Silk flow-diverting stent (Balt, Montmorency, France) treatment of giant ICA aneurysms.^23–25 A second-generation device, PED Flex, has recently been released with modifications to the delivery system. Published reports of experience with this new device are limited.^7,26 We feel that the more precise, controllable and open deployment would be easier than with the first-generation device.

Conclusion

GICAs frequently result in intractable cranial neuropathy that requires treatment. PED could be an option for these complex aneurysms in selective cases. However, the procedure-related morbidity and mortality rates of PED treatment of GICAs are at least 10%, which is higher than in the natural history of cavernous aneurysms in the literature. The treatment must be justified and accurately explained to the patient.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Beijing Municipal Administration of Hospitals Incubating Program (PX2020039).

ORCID iD

Xianli Lv https://orcid.org/0000-0001-8270-8464