Intracavernous de Novo Aneurysms without Prior Manipulation of the Harboring Vessel: Report of Two Cases

Intracavernous aneurysms of the cranial base, though less frequent than intradural intracranial aneurysms, can pose considerable therapeutic problems. To date, little is known concerning their spontaneous development and eventual growth kinetics. We report the observation of two de novo aneurysms without prior therapeutic manipulation of the vessels. In our first case, the 33-year-old woman had suffered from an intracerebral hemorrhage at the age of 22. At this time, neurosurgical evacuation was performed, neither angiographically nor histologically was an underlying vascular malformation disclosed. During follow-up observation 11 years later, a cavernous aneurysm of the right internal carotid artery was detected, together with an arteriovenous malformation of the left pericallosal artery next to the former hemorrhage. In the second case, the 49-year-old woman had undergone magnetic resonance imaging (MRI) for headache, revealing two intracavernous aneurysms of the right internal carotid artery. During follow-up, 7 years later, angiography disclosed a de-novo aneurysm of the left internal carotid artery, and an enlargement of the more distal right-sided aneurysm. Most cases of de novo aneurysm formation are described intradurally and after manipulation of the harboring vessel. In the patients presented here, therapeutically induced hemodynamic changes or vessel wall manipulations are not involved, pointing to a cerebrovascular predilection, that—in combination with a set of risk factors—leads to the development of cavernous aneurysms.


Introduction
Incidental intracranial aneurysms are seen in about 3% of the general population and are increasingly detected due to the vast availability of cranial imaging.
Whereas the detection of multiple aneurysms involving several intracranial vessels at first diagnosis is not uncommon, only few patients develop new aneurysms during follow-up of the initial aneurysm. Descriptions of this de novo formation of an aneurysm and introduction of the definition of these lesions as "aneurysms that develop unrelated to the origin of the initial aneurysm" date back to the 1960's [1].
Cavernous aneurysms present a distinct subgroup of intracranial aneurysms, since they predominantly occur extradurally, with a low risk for subarachnoid hemorrhage and rather predispose to carotid-cavernous fistulas or even massive epistaxis [2]. Treatment options comprise occlusion or sacrifice of the parent vessel, but with the advent of flow redirecting devices, vessel wall reconstruction without impeding the cerebral blood supply has become possible [3].
Most observations of de novo aneurysm development report intradural locations beyond the cavernous sinus [4] [5]. In many instances, prior therapeutical manipulation of cerebral vessels had been performed, eventually leading to alterations of cerebrovascular hemodynamics or to disintegration of the endothelial lining, which may trigger aneurysm formation. Identified risk factors comprise female gender, smoking habits, age under 40 years and arterial hypertension.
The angiographic detection of multiple intracerebral aneurysms and the location of an aneurysm in the carotid artery both enhance the risk of de novo aneurysm formation [6]. A general predisposition for developing cerebrovascular aneurysms or angiomas during lifetime has been related to diseases such as angiodysplasia or mural degeneration [7] [8].
Though cases without any previous intervention have been described, to the best of our knowledge, no case has been reported with de novo formation of an aneurysm in the cavernous carotid segment. In this article, we describe two cases of cavernous de novo aneurysm formation without prior manipulation of the parent vessel. The first case is related to a cerebral arterio-venous malformation.
The second is associated with multiple aneurysms at first diagnosis.

Patient cases
Cases of de novo formation of aneurysms without prior manipulation are rare, most reported cases are related to a therapeutic carotid occlusion, potentially altering hemodynamics and biomechanic properties of the arterial wall. In the two cases presented here, de novo aneurysm formation occurred in the cavernous sinus without prior manipulation of the cerebral vascular system. One patient was already harboring intracranial aneurysms; the other patient was simultaneously developing an arteriovenous malformation. Both findings are known to be associated with the formation of de novo aneurysms.
Concerning established risk factors for cerebral aneurysm formation, both patients were female, of young age and the internal carotid artery was involved [6].
Different from patient 1, patient 2 had multiple aneurysms and a history of smoking, while patient 1 presented with a concurrent AVM.
According to the sequential angiographies, two de novo aneurysm formations and one enlargement of a preexisting incidental aneurysm were observed. Assuming a hypothetical linear kinetic, de novo "aneurysm 1" grew almost 3 mil- unruptured intracranial aneurysms and co-existing AVMs [9]. In most cases, these aneurysms develop in the feeders of the AVM. Increased blood flow in the feeding artery is discussed as the main contributor to stress on the vessel wall, which then triggers the formation of aneurysms [10]. Further contributing factors may be lesser resistance in the feeding artery and increased hemodynamic Open Journal of Modern Neurosurgery turbulences.
Aneurysm location remote from the feeding artery has also been reported.
About 43% of the aneurysms have been described to be without anatomical relation to the AVM feeder and 20% to be proximal to its origin [11]. None of the aneurysms developed in the cavernous segment of the internal carotid artery.
In our case 1, there is no anatomical proximity between the cavernous aneurysm and the AVM, only a co-occurrence can be noted. Regarding the size of the AVM a flow related induction of the carotid aneurysm seems improbable, whereas a general predisposition of the intracranial vessels to develop wall abnormalities has to be discussed.
There are differing opinions about the ideal treatment strategy for co-existing abnormalities. In most instances, treatment of the aneurysm prior to the treatment of the AVM to prevent enlargement or rupture is suggested. It is assumed that sudden exclusion of the AVM leads to a drastic increase in vascular resistance of the feeding artery, adding a stressor on the aneurysm wall and the nearby upstream arteries. Since these vessels have adapted to the reduced ("stolen") flow, which beforehand drained through the AVM, a breakthrough bleeding can occur [12].
On the other hand, a decrease in size of feeding artery aneurysms after surgically removing the AVM has been observed and the resection of the AVM constitutes an alternative to treat both intracranial lesions [13] [14]. In our case 1, the aneurysm remained constant after resection of the AVM, pointing to local wall abnormalities underlying the development of the aneurysm, rather than to flow related induction.

Multiple intracranial aneurysms
In a meta-analysis concerning the formation of de novo intracranial aneurysms, multiple intracranial aneurysms at first diagnosis were identified as one of the independent risk factors [6]. This finding had been similarly described in a long-term follow-up study of patients after aneurysm clipping using computed tomography angiography (CTA) [15]. De novo aneurysms can be regarded as a special subset of multiple aneurysms, given the hypothesis of decreased arterial wall shear-stress resistance, affecting parts or even the entire cerebrovascular system [5].
In our case 2, multiple aneurysms had been present before development of the third aneurysm. Two of the three lesions showed an increasing size over 8 years follow-up, consistent with the concept of multifocal shear-stress resistance loss.
In addition, continued presence of hemodynamic risk factors such as nicotine consume or arterial hypertension suggest a lifelong process rather than a single event at the origin of the aneurysm formation [16].

Limits of the Study
Although in both patients the first angiographies did not detect the aneurysms, it remains questionable whether the aneurysm or a small vessel incoherence had Open Journal of Modern Neurosurgery already been present. Technical factors, individual observer experience or inadequate application of contrast agent can be reasons to miss a small forming aneurysm. Especially the discrimination between overlapping structures can be difficult. Technical advances such as three-dimensional reconstruction of the vessels help to reduce the risk of overlooking small abnormalities. In a follow-up screening after subarachnoid hemorrhage for the frequency of new aneurysms, CT-angiography was performed as imaging strategy. 59 apparently de novo aneurysms were detected and retrospectively; 68% of these aneurysms had already been detectable on prior CT-angiographies [16].

Conclusion
Cavernous de novo aneurysm formation without prior manipulation of the harboring vessel is a rarely observed phenomenon, probably associated with a cerebrovascular predisposition for reduced arterial wall resistance. Anatomical factors such as multiplicity of intracranial aneurysms or co-occurrence of aneurysms with cerebral arteriovenous malformations should prompt thorough and long-lasting follow-up using MR-angiography, to enable timely decision-making about safe treatment strategies.

Informed Consent
Both patients provided written informed consent prior to the therapeutic interventions in 2016 and 2018, respectively, to the use of personal health data for scientific research purposes.

Conflicts of Interest
The authors declare no conflicts of interest regarding the publication of this paper.