Blood Blister-like Aneurysms (BBA) are arterial lesions located in the anterior wall of the Internal Carotid Artery (ICA) without branches, lesions are most commonly found in the anterior wall of the ICA [5], but also in the dorsal wall [2, 5-8], distal medial wall [1], superior wall [9] and bed ventral side of the paracranial process [10]. BBA has also been reported in other intracranial arteries [11-13], but the original and most classic definition of BBA is limited to ICA. the typical morphology of BBA is a small hemispherical bulge [1,2]. bba is rare, with an incidence of approximately 0.9C6.5% of ICA aneurysms [1,14], 1% of all intracranial aneurysms [8], and 0.5C2% of all intracranial ruptured aneurysms [ 15,16]. BBA was first reported in the late 1970s [3] and was named “blood blister-like” aneurysm by Takahashi in 1988 [4].
1, Etiology and pathology of BBA
Gonzalez et al [17] searched the literature on BBA from January 1965 to July 2013 and found 63 papers and 322 patients, all with only observational case studies and case reports and no randomized studies, probably because of the sudden onset of the disease or its unclear pathophysiological etiology. Hemodynamic alterations and atherosclerosis are considered as the two most likely etiologies [18, 19]. Histological studies have shown that BBA is not a true aneurysm, but a fragile fibrin layer localized in the lumen of an artery, so that BBA does not have any relationship with arterial branches and has a high rate of bleeding [2, 3]. 40-89% of BBA is associated with arterial entrapment [9, 14, 20], which may be one of the mechanisms of BBA formation. Based on what was observed at the time of surgery, some authors have speculated that calcified changes in the vessel wall may be associated with BBA [17].
The reason why BBA is commonly found in the anterior wall of the ICA is unknown. Although other sites have been reported, such as the anterior cerebral artery [11,12,21], middle cerebral artery [21], and basilar artery trunk [22], it is unclear whether they share the same pathological basis, as only pathology of BBA in the anterior wall of the ICA has been reported, and there are no pathological reports to support that all these different sites are the same disease.Ishikawa et al [9] first reported the pathological autopsy of a patient who died after surgery, in which eccentric atherosclerosis of the carotid wall with marked intimal thickening was observed in and around a rupture point in the cross-section of the affected internal carotid artery. In the portion adjacent to the rupture point, the internal elastic layer in the border between the normal and sclerotic carotid walls suddenly disappeared, as did the middle layer of the vessel wall. The gap in the inner elastic layer is covered by fibrin tissue and the extravascular membrane, whereas in saccular aneurysms this part is usually composed of collagenous fibrous tissue. At the point of dissection, the extravasation was also torn and dispersed, no inflammatory cell infiltration was seen, and no arterial entrapment was observed. No such abnormality was found in other parts of the vessel wall, but there is no rational explanation as to why the disintegration of the inner elastic lamina occurs at the periphery rather than at the center of the atherosclerotic lesion.
2. Clinical manifestations of BBA
The mean age of patients with BBA was 50.6 years, and a high female prevalence (233 women, 72%), common right-sided ICA, and association with hypertensive disease were observed to be its characteristics.
The typical clinical presentation is subarachnoid hemorrhage (SAH). The age is young compared to patients suffering from saccular aneurysms [23], [19, 23]. In Gonzalez et al [17] reported that the clinical presentation was predominantly SAH at the initial stage in 319 cases (99%), presenting as intracerebral parenchymal hematoma in 1 case (0.3%) and headache without evidence of SAH in 2 cases (0.7%). 218 patients (68%) had more severe initial symptoms with a WFNS score greater than 3.
3 , Imaging diagnosis of BBA
In the imaging diagnosis of intracranial aneurysms, DSA and CTA have been able to differentially diagnose intracranial microaneurysms in recent years. [24-26]. However, the imaging diagnosis of BBA remains challenging, and sometimes it is difficult to detect a microscopic BBA on the first DSA or CTA images [27]. The evolution of imaging of a ruptured BBA requires special attention, as the lesion can develop into a cyst and rupture and bleed again after a few days [18]. Some authors suggest that hemisphericity may be the hallmark imaging feature of a BBA, while berry shape may indicate a saccular aneurysm. However, different literatures have also pointed out that the berry shape does not exclude the diagnosis of BBA because BBA may change from a hemispherical shape to a berry shape during the gradual absorption of the clot at the rupture site [6,18,23].
High-resolution MRI is helpful in the diagnosis of entrapment of the ICA carotid segment and intracranial arteries, and this examination allows the observation of intermural hematomas in cross-section [28,29].Nobutaka et al [30] reported a case of a young SAH patient suspected of BBA, which was not diagnosed definitively by two DSA within a short period of time, and performed high-resolution MR, which showed both T1- and T2-weighted images in the local vessel wall with The T1- and T2-weighted images showed a significant high signal shadow in the local vessel wall, suggesting an intermural hematoma. A third DSA and subsequent surgical procedure confirmed the diagnosis of BBA. Although MR may be helpful in the diagnosis of BBA in the subacute phase, the intensity of MR signal in hematomas varies considerably between periods, so MR findings should be evaluated with caution. patients, suggesting that CTA does not serve the purpose of definitive diagnosis and assessment of postoperative outcome.Regelsberger et al [31] also concluded that conventional angiography should be preferred over MRA and CTA in patients with subarachnoid hemorrhage, and that all four angiograms and 3D techniques can further help to detect small arterial bulges.
Although it is difficult to determine the diagnostic imaging criteria for BBA, Liu et al [32] proposed six diagnostic criteria, including (1) aneurysm located in the superior segment of the bed prominence of the ICA protruding anteriorly; (2) no branching; (3) initially small aneurysm (maximum diameter <10 mm); (4) aneurysm consistent with the site of SAH bleeding; (5) repeat vascular imaging within 2 weeks (CTA, MRA, and DSA) within 2 weeks revealed rapid aneurysm growth; (6) aneurysm or aneurysm-carrying artery with irregular walls. The diagnosis of BBA can be made by meeting any one of the 5 or 6 diagnostic criteria, provided that the diagnostic criteria 1 to 4 are met, of which the 5th and 6th are important for definite diagnosis.
4 . Treatment of BBA
Treatment of BBA is as difficult and challenging as the diagnosis because the extremely fragile “wall” of BBA makes it complex and dangerous to treat. before and one year follow-up after treatment [33]. In contrast, for perioperative BBA, 46% of endovascular treatment approaches and 21% of surgical approaches require reintervention because of re-rupture and bleeding of the aneurysm or evidence of a growing aneurysm [17]. The difference between saccular aneurysms and BBA suggests that the latter are aggressive in nature and require a more complex treatment approach. 303 patients with BBA reported by Gonzalez et al [17] underwent surgical or endovascular treatment; 28% of patients failed the first treatment approach and 86% of them received a second treatment, representing 23% of the total number of patients; 48 cases proved to be recurrent and 56% of them received a second treatment Of these, 56% received a second treatment, accounting for 15% of the total number of patients. Aneurysm occlusion or stabilization was achieved in 19 patients who received a third treatment. All treatments included 268 surgical, 147 endovascular, and 19 conservative treatments (some patients received more than one treatment), 78 (24.5%) had perioperative complications (bleeding or ischemic complications), the overall mortality rate was 19% (61), and the disability rate (MRS score >2 or reported postoperative neurological deficits) was 17% (55). 55 cases). Japanese national statistics [34] showed a 43% intraoperative rupture rate and a 25% mortality rate in acute phase BBA surgery. The very high rate of secondary surgery or salvage treatment, disability, and mortality shows the complexity of BBA treatment.
4.1 Surgical treatment of BBA
Gonzalez et al [17] reported eight different surgical approaches in 40 papers (Table 1), with craniotomy clamping being the most common approach, accounting for 80% of patients operated on, of which 30% experienced perioperative complications. Other treatments were added in 44 cases (21%) to ensure safety or to occlude the BBA. Surgical isolation was the second commonly used approach and was the primary or salvage treatment in 61 patients (Table 2). In total, aneurysm regrowth was observed in 10 cases (5%), and rebleeding occurred in 63 cases (30%). Salvage treatment after rebleeding or regrowth included a second attempt at clamping, arterial suturing, spring-ring embolization, stent-assisted spring-ring embolization, endovascular or surgical isolation with or without bypass, or bypass only. The most common surgical salvage methods were isolation without bypass (11 cases) and arterial suture (10 cases). There were 45 (18%) overall surgical complications and 35 (14%) deaths. The mortality rates for each treatment were: 57 (75% of total mortality in the surgical group) for clamping, 4 (5%) for wrapping, 7 (9%) for surgical isolation without combined bypass, 5 (7%) for bypass combined with surgical isolation, 1 (1%) for bypass combined with endovascular isolation, 2 (3%) for arterial suture, and no deaths in patients who received bypass alone.
4.1.1 Clamping
Direct clamping of the BBA using an aneurysm clip was first reported, but the risk of severe intraoperative and postoperative rebleeding has been reported several times [8,23,35,36]. Intraoperative rupture occurs when the BBA tears and ICA tears during separation of the aneurysm, and gradual slippage of the aneurysm clip clamped to the thin aneurysm neck [8,23]. Postoperative rebleeding may be caused by torsion or slippage of the aneurysm clip, incomplete clamping, or incomplete clamping of the aneurysm clip to the vessel at the lesion on the aneurysm-carrying artery leading to BBA regrowth [37]. Some authors have suggested the use of parallel clamping, which intentionally clamps a portion of the normal ICA wall, causing a mild local stenosis, but with the risk of ischemic complications [8,18,23,36,38].
4.1.2 Encapsulation
Because of the high risk of direct clamping, some authors believe that instead of taking such a big risk it is better to strengthen the outer wall of the fragile weak area using various materials to reduce the risk of rebleeding as well as to create opportunities for secondary surgery [2,9,39]. However, Ogawa et al [23] concluded that wrapping did not prevent rebleeding from BBA and was significantly associated with a high incidence of postoperative rebleeding and mortality.
4.1.3 Surgical isolation
Isolation of the aneurysm by occlusion of the aneurysm-carrying artery using either an endovascular approach or a surgical approach requires a rigorous preoperative assessment of the potential for ischemic events. However, the assessment of neurological function in patients with SAH is unreliable due to the deterioration of clinical neurological function and the use of sedative drugs. In addition, angiography to assess collateral circulation does not guarantee that sacrificing ICA is safe [5]. The use of balloons to perform occlusion tests frequently produces false-negative results, and 2-22% of patients with permanent internal carotid artery occlusion who are able to tolerate carotid occlusion ischemia tests (using SPECT, Xenon CT, TCD examinations) are at risk for immediate ischemic complications [40-43]. Similarly, there is a risk of delayed cerebral ischemia.
4.1.4 Intracranial extracranial bypass
The extracranial bypass technique was first applied by Donaghy and Yasargil in 1967 in the treatment of ischemic stroke [44]. Despite the ineffectiveness of international randomized clinical trials for the prevention of ischemic stroke, some progress has been made in this technique with the use of different graft materials, adaptation and refinement of protective measures during the temporary blockade period [45,46]. However, there is still no reliable assessment method to prove that sacrificing the aneurysm-carrying artery alone or combined STA-MCA bypass is safe in the acute phase of SAH.
4.1.5 Arterial suturing
In neurosurgery, where vascular perforation can occasionally occur or laceration of the aneurysm neck during clamping of the aneurysm, Yasargil first suggested that arterial suturing could be performed, and some successes have been reported [1,23,47], although, of course, there have been reports of catastrophic consequences after using this technique [18, 39]. This is a surgical approach that is extremely demanding in terms of technique and equipment and has been reported internationally in only a few medical units.
4.2 Endovascular approach for BBA
Not only surgical procedures are subject to different controversies regarding various treatment methods, but the application of various endovascular treatment methods also faces the same situation [16,22,32,48-50]. 87 patients were reported in 26 papers using endovascular methods for BBA summarized by Gonzalez et al [17] (Table 3). Regrowth occurred in 33 cases (38%) after the first treatment, rebleeding occurred in 11 cases (12.6%), and 32 cases (36.8%) required a salvage second treatment. The most frequently used method of treatment by the endovascular approach was stent-assisted spring-ring embolization (30 cases, 34.5%). The overall disability rate was 3.4% (3 cases) and the mortality rate was 11.5% (10 cases) in patients treated with the endovascular approach as the first treatment. The mortality rate was 21.7% (5/23) in patients treated with spring-ring embolization; no deaths in patients treated with spring-ring or balloon occlusion of the aneurysmal artery; 10% (3/30) with stent-assisted spring-ring embolization; 33.3% (1/3) with overlapping stent embolization; 7.7% (1/18) with multiple stent embolization; and no deaths with single or There were no deaths with single or multiple flow-guiding devices.
4.2.1 Spring-ring embolization for BBA
Due to the small size of BBA and the wide neck of the aneurysm, direct spring-ring embolization is not indicated [51]; spring-ring embolization should be performed only after the BBA has enlarged to a cystic aneurysm.Ezaki et al [52] performed craniotomy for aneurysm isolation on day 15 after the first bleeding in an enlarged BBA. , the aneurysm disappeared. Similar reports have been made by other authors [51,53]. Park et al [50] performed spring coil embolization of an aneurysm with an enlarged to cystic aneurysm, and when the second coil was released, the aneurysm ruptured, and the coil was continued until the aneurysm did not appear. The aneurysm recurrence was still seen on the repeat angiogram 12 months after surgery. In another case of BBA with enlarged to cystic aneurysm, spring coil embolization was used, and recurrent aneurysm rebleeding was also seen on the 6th day after the procedure.Islam et al [54] reported a case of BBA in which recurrent aneurysm was also found on review angiography 3 months after GDC embolization. Therefore, the long-term results of spring-ring embolization alone for BBA are poor.
4.2.2 Stent-assisted spring-ring embolization for BBA
Fang et al [32] used stent-assisted spring-ring embolization for BBA in 5 cases, and 4 patients had a better postoperative period, but the aneurysm enlarged again during postoperative follow-up, suggesting that stent-assisted embolization of aneurysms can reduce the rebleeding rate and mortality, but not achieve a curative effect, and the application of stent-assisted embolization technique can prevent rebleeding and reduce the impact of blood flow on the aneurysm wall.Lim et al [55] used stent-assisted spring-ring embolization in 3 cases, aneurysm recurrence occurred within a short period of time after the procedure; 5 cases (2 of which were recurrent aneurysms) were switched to double-stent overlay-assisted spring-ring embolization, and complete cure of the aneurysm was found at follow-up, and they concluded that reconstruction and reinforcement of the aneurysm-carrying artery wall is the key to the treatment of BBA.
4.2.3 Overmolded stent embolization for BBA
Theoretically, overlapping stents are ideal for the treatment of BBA because they treat the aneurysm and ensure normal blood flow. The BBA is located in the superior segment of the bed of the internal carotid artery, and the current overlapping stent has poor compliance, which makes it difficult to pass through the siphon segment, and then barely passes through the thin aneurysm wall, resulting in aneurysm rupture. Another problem is that the BBA is located adjacent to the anterior choroidal artery and the posterior communicating artery, and it is difficult to avoid these vessels and cover only the aneurysm neck, so it can only be used selectively in some specific cases. In addition, the high rate of late-onset internal carotid artery trunk occlusion after stent placement is one of the reasons that limit the widespread use of overlapping stents.
4.2.4 Stent embolization alone for BBA
For aneurysms intended for stent-assisted spring-ring embolization, if the intra-aneurysmal space is too small for further embolization after stent release and internal carotid artery embolization is not suitable, simple stent implantation is often used to treat the aneurysm to end the procedure. filorlla et al [56] reported two cases of BBA successfully treated with simple stents, with good results with single and double stents, respectively. Among the two cases treated with simple stenting by Yibin Fang et al [57], one case had rebleeding on the second postoperative day and eventually died after resuscitation, and one case had a long-term stable aneurysm treated with simple stenting, which suggests that the choice of simple stenting for BBA in the acute phase needs to be cautious.
4.2.5 Blood flow-directed device embolization for BBA
The flow-guided device is a new endovascular device originally designed to treat large/wide carotid aneurysms, coarctation/spinous aneurysms, or very small aneurysms. The flow-guided device is based on two principles: (1) altering the pattern of inward and outward blood flow within the aneurysm, thereby reducing the velocity, turbulence and wall shear stress, reducing the blood flow within the aneurysm sac to a stagnant state, increasing the viscosity of the blood, forming a thrombus within a few weeks, further disrupting the blood flow within the aneurysm, and gradually embolizing it completely; and (2) chronic stimulation of the vessel wall by the metal-covered network, inducing new endothelial proliferation, and ultimately wrapping the flow-guided device into the aneurysm. Eventually, the flow-directing device is wrapped into the diseased vessel wall, repairing the diseased aneurysm-carrying artery and keeping the collateral or through-branch flow open [58]. Because it has lower porosity and higher metal coverage than conventional intracranial self-expanding stents, it has higher flow-guiding ability, which can reduce the blood flow into the aneurysm lumen, promote the formation of intra-aneurysmal thrombus and eventually lead to the occlusion of the aneurysm lumen with thrombus formation, while the stent-induced intimal hyperplasia promotes the healing of the aneurysm-carrying artery and the aneurysm neck.
Aydin et al [59] treated 11 patients with BBA (9 in the ICA bed segment and 2 in the basilar artery) with the SILK flow-guided device in the acute phase, with a mean treatment time of 9.6±3.6 days. After placement, stent malapposition occurred, and one Enterprise self-expanding stent was immediately used to perform the stent overlay. No procedure-related complications occurred in all patients. Immediate postoperative imaging showed residual tumor neck in one case and residual tumor cavity in the remaining 10 cases. The mean time to first postoperative DSA review was 9.7±3.6 days, with one case achieving complete embolization, one case with residual neck, and nine cases with residual lumen. one patient with H-H grade 4 died of sepsis at 12 days postoperatively. During the follow-up period, one patient stopped taking antiplatelet drugs on his own and had a cerebral ischemic event at 23 days postoperatively, and DSA showed occlusion of the aneurysm-carrying artery, because the anterior communicating artery was well compensated and no serious cerebral ischemic event occurred during the follow-up period. The remaining nine patients had a complete occlusion of the aneurysm on DSA at 3 months postoperatively, and mild in-stent stenosis (<20%) occurred in two patients. At 6-month postoperative follow-up, all patients had no aneurysm recurrence and all achieved an mRS score of 0-2.
Chalouhi et al [60] successfully treated eight cases of BBA using the PIPELINE flow-guided device; five of the patients had subarachnoid hemorrhage, one had anterior headache, and two were incidental findings. The size of the aneurysms averaged 2.5 mm, 7 were located in the ICA and 1 in the basilar artery. All patients did not experience any complications during the perioperative period. At clinical follow-up, good results were achieved in all 8 cases (mRS score 0-2). 6 patients received angiographic follow-up, 5 had aneurysm occlusion, and 1 had a significant reduction in aneurysm size.
5, Choice of BBA treatment method
About one-fourth of patients have combined perioperative bleeding or ischemic complications during the treatment of BBA. The perioperative complications and mortality rates of surgical treatment of BBA were 21% and 17%, respectively, and the perioperative complications and mortality rates of surgical treatment of intracranial aneurysms in the ISAT study were 36.4% and 8.3%, respectively, indicating that the risk of surgical treatment of BBA is much higher than that of saccular aneurysms [17,34]. In contrast, the complications and mortality rates of the endovascular approach for BBA were 3.4% and 11.5%, respectively, which are significantly lower than those of the surgical approach [17].
The perioperative complications and mortality rates of BBA are high regardless of the treatment method used, but in comparison the complications and mortality rates of the endovascular approach are significantly lower. The use of multilayer flow-directed devices for BBA appears to be a promising approach with reconstruction of the aneurysm-carrying artery, avoiding endoluminal treatment of the aneurysm and possibly being more hemodynamically compatible. Its main drawbacks are the need for dual antiplatelet therapy and concerns about occlusion of the penetrating vessel. More than 10 cases of BBA treated with multiple flow-directed devices have been reported, with no reports of clinical symptoms due to occlusion of the penetrating vessel. On the other hand, although imaging occlusion of the ophthalmic artery has been reported in more than 25% of patients at 1-year postoperative review [61], there were no clinical symptoms, suggesting that flow-directed devices are safe and effective in the treatment of BBA.
6 .Summary
Little is known about the etiology and pathology of BBA. Regardless of the treatment technique used, BBA is more prone to intraoperative complications than saccular aneurysms, and BBA is prone to regrowth and rebleeding after surgery. Endovascular treatment has a lower mortality rate compared to surgical approaches. Multilayer flow-directed devices appear to be a promising approach. Surgical clamping after failed endovascular treatment is also an effective surgical approach. The choice of treatment for BBA will depend on the experience of the neurosurgical and neurointerventional teams at the center, and timely treatment and close imaging follow-up are important for patient prognosis.