**2. General features and clinical presentation**

Blister aneurysms are a distinct form of cerebral vascular lesions with often mixed characteristics and uncertain pathogenesis. They comprise less than 2% of all intracranial aneurysms [1]. Originally described by Sundt and Murphey more than

40 years ago [2], the typical configuration of blister aneurysms consists of a shallow and broad-based or even semifusiform focal protrusion located on the internal carotid artery [3]. Arising from the anteromedial carotid wall in up to 65% of cases [4], these lesions seem to be unrelated to major arterial junctions, although very fine branches such as those supplying the optic nerve may sometimes be involved [5]. Rarely, blister aneurysms can be found on the anterior communicating artery or even the basilar trunk [6, 7], while in a recent case report, the posterior inferior cerebellar artery has also been implicated as another potential site of origin for such a lesion [8].

A prominent characteristic of blister aneurysms is the marked weakness of their wall, a feature that not only reflects the unique pathology of these lesions but also predetermines their high rupture risk, aggressive clinical course, and tendency for rapid growth and progression. In the most common scenario, a blister aneurysm will be diagnosed after an episode of subarachnoid hemorrhage (WFNS grade > 3 in 68% of cases) [9]. Being initially small and sessile, it will substantially enlarge within days of presentation, reaching finally a shape much similar to that of its saccular counterparts [4]. Commonly, the end result is a rerupture with potentially catastrophic consequences for the patient.

On a side note, and regarding terminology, blister aneurysms were originally known as dorsal, anterior or superior carotid wall lesions, a nomenclature though that soon became obsolete failing to recognize the presence of such anomalies on the medial, posteromedial or lateral surface of the internal carotid artery [10]. Additionally, intracranial vessels have never—by tradition—been designated as dorsal or ventral, adding another reason to abandon at least the first of these denominations [11]. An alternative, broader term used mainly by Japanese authors was carotid trunk aneurysms [4]. Still, confusion remained since bleb-like but essentially stable carotid lesions have been encountered during surgery, an observation that clearly indicates that not all such morphological entities fulfill the requirements to be considered as true blister aneurysms, and as a matter of fact, some of them may even be the precursors of typical berry lesions [12, 13]. Whatever the case, the term blister (or blister-like) aneurysms seems to be by now the dominant one within the relevant literature and as such will be used throughout the present manuscript.

## **3. Epidemiology and demographics**

Blister aneurysms are rare lesions comprising less than 2% of all intracranial aneurysms [1] and 0.9–6.6% of internal carotid artery lesions [14]. In the three largest series published to date, Yaşargil et al. reported 3 blister aneurysms in a total of 319 carotid lesions [15], Nakagawa et al. reported 8 cases in a series of 460 surgical patients [3] and Meling et al. reported 14 lesions in a total of 912 aneurysms [16].

Having a slight female preponderance and occurring more frequently on the right side, blister aneurysms tend to affect patients at a rather younger age than their saccular counterparts [17, 18]. In a series of six patients, Abe et al. found a mean presentation age of 56 years [11], while Park et al. calculated this in their own cases at 35.4 years [19]. Risk factors include arterial hypertension [6] and atherosclerosis [16].

#### **4. Pathological considerations**

Due to the rarity of blister aneurysms, our understanding of the relevant pathology is only limited. For most authors these lesions are of a dissecting nature [20], and, as such, they are considered to be the consequence of a tear in the affected artery's inner wall followed by intramural hemorrhage [21, 22]. The resultant protrusion is

#### *Blister Aneurysms DOI: http://dx.doi.org/10.5772/intechopen.89284*

covered by only the adventitial layer. At this point, it should be noted that the adventitia of intracranial arteries is well known to be thicker over bifurcation sites, partially compensating for the underlying medial defect. Arising exclusively at nonbranching arterial segments, blister aneurysms lack this relatively rigid coverage and are thus much more fragile than their saccular counterparts [23]. This difference between the two accounts for the prominently aggressive clinical course of blister lesions (i.e. increased risk of bleeding and tendency for rapid subsequent growth and rerupture). In their series of 40 blister aneurysms, Ogawa et al. found signs of dissection (double lumen, arterial narrowing or dilation, etc.) in 10 cases [4], while Satoh et al. reported a similar association in as many as 16 out of their 18 in total patients [13].

An alternative hypothesis on the pathology of blister aneurysms is that they are in fact false lesions, essentially representing a focal arterial wall defect [8]. In this direction, Abe et al. suggested a few years back that the characteristic bleb-like protrusion seen by surgeons in such cases is nothing more than an organized blood clot covering the diseased arterial site [11]. Removal of this clot during surgical preparation of the aneurysmal dome is highly likely to cause a rerupture [4]. The pseudoaneurysm theory was initially based on macroscopic intraoperative findings but was later confirmed in at least two cases reported by Charbel et al. [24]. According to these authors, pathological examination of the aneurysmal sacs, which were resected in both cases, in their entirety revealed only blood clot and no fibrous, elastic or smooth muscle tissue (Verhoeff-vanGieson staining plus immunostaining) [24].

The first-ever complete microscopic description of a blister aneurysm has been delivered by Ishikawa et al. in their, classic by now, publication in neurosurgery in 1997. To do this, the authors of the article applied an Elastica Masson stain on cross section specimens of the internal carotid artery of a patient who sustained a fatal rupture of such a lesion [25]. According to their report, the examined blood vessel was heavily atherosclerotic with prominent underlying thickening of the intima. Near the edge of the atheromatous plaque, both the internal elastic lamina and the tunica media were abruptly terminated, and the resultant gap (i.e. the aneurysm sac) was covered only with fibrinous tissue and adventitia. The latter was neither thickened nor rich in collagen as is usually seen in a saccular aneurysm. At the rupture point, the adventitia was lacerated and fragmented. Notably, and contrary to what it would be expected in a dissecting lesion, no inflammatory infiltration or dissection of the artery outside the actual aneurysm was observed.

In a more recent publication, Kim et al. reported a blister aneurysm with a typical clinical course whose dome was resected during surgery for histologic examination. Their conclusions, although interesting, seem to have only added to the confusion: immunohistochemical staining for smooth muscle actin proved to be positive, a finding compatible with an intact tunica media and thus a true lesion. Medial fibroblast proliferation and laminar thrombosis were also noted [26].

It is obvious that the literature on pathology of blister aneurysms has been, up until now, far from conclusive. Speculations stray widely with data supporting each theory being only limited. A possible explanation is that we are dealing with different stages of a rapidly evolving disease or, alternatively, that there is no single entity but a whole range of these. Our only certainty seems to be that morphological changes taking place in blister aneurysms are much more destructive than those seen in berry lesions.
