**7. Clipping of solitary unruptured aneurysms**

*New Insight into Cerebrovascular Diseases - An Updated Comprehensive Review*

but also the patency of the surrounding normal vessels.

used to estimate these phenomena [65–67].

tured counterparts [70].

currence, and rerupture.

**6. Hemodynamic consequences of aneurysm clipping**

fluorescence angiography to not only verify the occlusion of the aneurysmal sack

The hemodynamic characteristics of intracranial aneurysms are thought to play a pivotal role in their development, evolution, and eventual rupture, interfering and modifying the local biology of the vascular wall [61–63]. The theory suggests that the wall is exposed to a higher degree of sheer stress than it can physiologically withstand. This leads to a local weakening and abnormal remodeling, which in time will form an aneurysm. Its growth can be a result of local proliferation of mural cells, a distention of the cellular and intercellular structures, or possibly a mixture of the two. A meticulous in vitro study affirmed that growth cannot be entirely the result of simple fluid physics [64], a non-Newtonian model being more precise in ascertaining the altered hemodynamics in intracranial aneurysms [65]. However, as it is impossible to perform direct measurements on hemodynamic stress in patients or living experimental models, methods implying computational fluid dynamics are

Aneurysmal rupture results from the mechanical weakening of the arterial wall that is subsequently unable to contain the force of the flowing blood [68]. The wall sheer stress is defined as the tangential frictional force that the blood exerts upon the endothelium, being the highest at the neck and the apex of the aneurysm [65]. The innerworkings of endovascular procedures are closely linked to these hemodynamic conditions, as the presence of a coil determines alterations in wall shear stress and blood flow that conclude with the intraluminal thrombosis of the aneurysm [69]. In MIA, wall sheer stress is apparently increased in UIAs distal to a ruptured aneurysm after treatment, whether surgical or endovascular, leading to a theoretical rise in the risk of rupture [66]. Moreover, also in MIA, ruptured aneurysms may possess a more irregular shape, larger size, and dometo-neck ratio, as well as a lower minimum wall shear stress than with their unrup-

After clipping, a series of local and distal changes in hemodynamics may occur.

Nevertheless, these are not as intensely analyzed as for untreated aneurysms. Successful surgical obliteration of the aneurysm results in the complete cessation of blood flow inside the lumen. However, it is not clear what impact the presence of the aneurysmal clip itself has on the wall shear stress or its effects on the vascular wall. A residual neck (i.e., a portion of the neck that was not occluded by the blades of the clip) may in time lead to aneurysmal regrowth, depending on the size of the remnant as well as its location [71]. Apparently, a distal remnant is at a higher risk for aneurysmal regrowth than a proximal residue. Therefore, it is crucial to ensure an adequate placement of the clip during surgery and to adjust its position if required. The alterations in dynamic flow can also be observed systemically after clipping or coiling, especially in the period after vasospasm caused by aneurysmal rupture [72]. In the study conducted by Inoue et al., patients treated by coiling presented a significantly lower cardiac index, as well as a significantly higher systemic vascular resistance index than the group managed via clipping, although this might have been the result of systemic therapy for managing vasospasm and aggressive volume loading rather than of the procedure itself, especially as the patients in the coiling group arrived in a worse neurological state than those of the clipping group. Needless to say, more studies are required to discern the actual impact that clipping has on the cerebral vasculature, especially concerning aneurysmal regrowth, reoc-

**156**

The cerebrovascular diseases causing such controversy in regard to treatment are few in number [73]. The reasoning behind this continuous debate is that the prophylactic management of UIAs must be justified by a suitable procedurerelated outcome when compared to the anticipated natural history [74]. Despite clipping once being the management centerpiece, the swift refinement of endovascular procedures and innovation of flow diversion devices have steadily replaced surgery as the first line of therapy for UIAs. However, certain countries still favor clipping due to its longevity, effectiveness, and the lower risk of recanalization than endovascular techniques, as well as lower procedure-related costs [75–77]. Consequently, whereas older patients who are unsuitable for surgery may benefit the most from endovascular procedures, clipping is considered preferable for younger patients with lower-grade aneurysms and that may be able to tolerate this intervention [76, 78]. The unruptured intracranial aneurysm treatment score (UIATS) provides a fast and easy method of triaging between the two treatment options; however, it has not yet been prospectively tested on patients harboring UIAs [79].

Studies such as ISAT, ISUIA, and UCAS are among the most cited concerning aneurysm treatment and natural history. The first of these revealed superior 1-year clinical outcomes for ruptured aneurysms by coiling in comparison to clipping, yet these results cannot be accurately extrapolated to clipping of UIAs [80]. The conditions in the unruptured setting are more advantageous, as the purpose of therapy is to ensure lifelong protection against aneurysm rupture, whereas the treatment of ruptured lesions is to allow survival of the patient during the acute phase of SAH without rebleeding or postoperative morbidity. Likewise, MCA aneurysms, which are generally considered more easily approached by surgery, were grossly underrepresented in this study. Several authors obtained much higher rates of complete obliteration via clipping than through endovascular procedures for aneurysms in this location [77, 81, 82]. This is more likely a consequence of the particular configurations of MCA aneurysms, rendering it more difficult to completely occlude the neck via endovascular procedures (wide-necked, possessing a small dome-to-neck ratio, the neck encompassing one of the arterial branches, etc.) [77]. Moreover, these aneurysms are generally adjacent to or surrounded by small perforators that may prohibit the use of stents. This technique also has the fundamental drawback of postprocedural thromboembolic events that may ensue at a higher frequency [83, 84]. In the largest multicenter study of very small UIAs treated via surgery, Bruneau et al. showed that the lesions found distal to the M1 segment were the safest to treat [85]. Despite additional enquires being required to reach a definitive conclusion, it is still worth regarding surgical clipping as the principal treatment modality for UIAs of the MCA.

Aneurysms of the anterior communicating artery are the most frequently reported in a large number of studies, possessing a higher risk of rupture than other locations while also being amenable to both endovascular and microsurgical techniques [36, 74, 86–89]. The term may actually be overly broad, also including aneurysms of the A1 and A2 junctions of the anterior cerebral artery or belonging entirely to these two segments, but being indistinguishable from true ACoA aneurysms on angiographic studies [88]. This location represents a genuine challenge for either approach. On the one hand, microvascular clipping is made difficult by depth, presence of perforators, and placement along the midline, implying increased cerebral traction in the absence of adequate relaxation [87, 89]. On the other hand, certain intrinsically unfavorable characteristics of aneurysms found in this location, such as a small dome, wide neck, multiple adjacent perforators, acute vessel angles, complex morphology, or posterior projection, can hinder

endovascular procedures as well [74, 90]. In their systematic analysis, O'Neill et al. discovered that coiling delivers the most favorable clinical results, while stentassisted coiling produced the highest incidence of treatment-related morbidity, without improving the rates of angiographically detectable recurrences or retreatment [74]. However, microsurgical clipping offered the most definitive aneurysm repair of the three methods and significantly lower rates of recurrence or reintervention. The best course of action for UIAs of this location remains to be decided.

UIAs of the internal carotid artery, including its smaller branches such as the anterior choroidal artery, ophthalmic artery, hypophyseal artery, and artery PCoA, are also fairly common, some sources citing them as the second most frequent after aneurysms of the ACoA [36, 91, 92]. Because the parent artery is located in proximity to the skull base, the surgical access of these aneurysms is often difficult. In order to address this issue, and many others, the first flow diverter device sanctioned for use was in 2011, being designated for wide-necked intracranial aneurysms of the ICA in adults [37]. Fortunately, small aneurysms of the cavernous segment generally present a low risk of rupture [73]. Therefore, taking into consideration the hemorrhage rates described by ISUIA for aneurysms of this location, it is generally not advisable to treat asymptomatic lesions smaller than 5 mm in any way [39, 73]. Aneurysms larger than 7 mm or those that are symptomatic can be safely treated by either method with satisfactory postoperative results. Once again, endovascular procedures are less invasive, but microsurgical clipping yields a higher rate of complete occlusion [93]. Despite this, due to the hemodynamic charge of the ICA, it is possible that pulsations, differences in wall thickness, and tension may cause clip rotation [94]. Additionally, after retractors are removed, the ensuing brain shift may determine additional kinking and subsequent stenosis of the anterior choroidal artery. ICA bifurcation aneurysms are generally scarce and, as a result, underrepresented in large prospective observational studies, leading to an enigmatic natural history [93]. For aneurysms of the paraclinoid ICA or of the ophthalmic artery, it is advisable to remove the anterior clinoid process to ensure better access and proximal control. This also alleviates the risk of causing postoperative visual disturbances, which represent a common complication of ICA aneurysm management, especially for this segment [95]. Using a bone microrongeur or an ultrasonic aspirator to perform piecemeal removal of the anterior clinoid instead of a high-speed drill leads to fewer such complications [95, 96]. Small UIAs of the paraclinoid ICA that are medially pointing can also be safely approached from the contralateral side, thus diminishing the need of mobilizing the optic nerves as well as of performing anterior clinoidectomy [97]. As a remark, appropriate selection of therapeutic method for unruptured aneurysms of the ICA and its branches should factor in the individualities of the lesions themselves. Ideally, a hybrid unit would allow either approach and the possibility of converting an endovascular procedure into an open surgical intervention in the case of intraprocedural complications (**Figure 3**).

Aneurysms of the posterior circulation, including the basilar artery apex or the posteroinferior cerebellar artery (PICA), have a much higher propensity to rupture [36, 73, 98]. Therefore, a conservative approach would be inadvisable for UIAs of this location. However, there is little data comparing the endovascular and surgical treatment of posterior circulation UIAs. After ISAT and the ensuing paradigm shift, there has been a scarcity of microsurgical reports on basilar apex aneurysms. Tjahjadi et al. reported a significantly higher rate of good and fair outcome (71 and 16%, respectively) after surgery of UIAs of the basilar apex than after clipping of ruptured lesions of the same site (49 and 19%, respectively) [99]. Nanda et al. also reported good outcomes following microsurgical clipping (71.9%) and asserted that a non-dominant PCoA (especially if hypoplastic) can be safely divided in the perforator-free area as to allow additional retraction of the ICA [100]. ISUIA revealed similar clinical outcomes for the patients recruited; however, the

**159**

**Figure 3.**

*flow.*

effective method of the two [108].

*Preventing Rupture: Clipping of Unruptured Intracranial Aneurysms*

endovascular procedures only achieved complete occlusion in approximately half of the cases treated [50, 101]. In contrast, aneurysms of the PICA (and to a certain extent the vertebral artery—VA) are still primarily treated via clipping due to their wide necks, generally multilobulated and nonsacular characteristic, thrombosed lumens, emerging arteries, or distal locations that render coiling substandard [102]. The lower cranial nerves encountered in the surgical field can easily and securely be avoided, especially via the transcondylar approach [103]. Moreover, cases in which microsurgery should be more fervidly supported number those with unfavorable endovascular access, very small aneurysm domes, or contraindications for stent usage (intolerance to dual antiplatelet therapy, nickel allergy, etc.) [85, 101].

*Illustrative case 1. (A) Preoperative CTA of a 21-year-old male with an incidentally discovered aneurysm of the right internal carotid artery (paraclinoidal segment). Video 1 is available at: https://bit.ly/2Z8W6rm. We used a right frontolateral craniotomy and approached the aneurysm via the Sylvian fissure. We drilled the anterior clinoid process, but the aneurysm ruptured during initial attempt at clipping. Because of its sheer size, we used three fenestrated clips to occlude the aneurysmal sac. The patient was discharged with no neurological deficit. (B) MRI scan, TOF sequence, at 1-year follow-up, showing the presence of the clip and no intraluminal* 

The previously mentioned UCAS and ISUIA are regarded as the most prudently devised large studies vis-à-vis the natural history of UIA, with numerous guidelines having been published in their wake in order to improve management decisionmaking [78]. However, imaging control was not compulsory in ISUIA; therefore, it could not tackle the possibility of aneurysms eventually changing their morphology or size. Moreover, there is the question of the UCAS not being relevant for populations outside Japan. There are still centers that recommend treatment for all small aneurysms possessing risk of developing SAH, the presence of a daughter sack or multiple aneurysms [78, 104]. After the ISAT was published, endovascular techniques gained a boost in popularity in the USA for both ruptured and unruptured aneurysms, overtaking surgical treatment in number of procedures performed [105]. Previous analyses show that coiling was associated with fewer complications, lower mortality, faster hospital discharge, and significantly lower costs than clipping [105, 106]. However, in centers outside the USA, where hospitalization, procedure, and nursing costs are lower, the differences concerning patient expenses are smaller. In South Korea, it seems that coiling is more expensive than clipping for UIAs, and this may also be available for developing countries [106]. The principal reason for this is the cost of endovascular implantable devices themselves (stents, coils and flow diverters, etc.), constituting more than 50% of procedure-related costs [107, 108]. Even so, a previous meta-analysis concluded that coiling generated a higher independent outcome and lower mortality rate, being the more cost-

*DOI: http://dx.doi.org/10.5772/intechopen.88038*

#### **Figure 3.**

*New Insight into Cerebrovascular Diseases - An Updated Comprehensive Review*

endovascular procedures as well [74, 90]. In their systematic analysis, O'Neill et al. discovered that coiling delivers the most favorable clinical results, while stentassisted coiling produced the highest incidence of treatment-related morbidity, without improving the rates of angiographically detectable recurrences or retreatment [74]. However, microsurgical clipping offered the most definitive aneurysm repair of the three methods and significantly lower rates of recurrence or reintervention. The best course of action for UIAs of this location remains to be decided. UIAs of the internal carotid artery, including its smaller branches such as the anterior choroidal artery, ophthalmic artery, hypophyseal artery, and artery PCoA, are also fairly common, some sources citing them as the second most frequent after aneurysms of the ACoA [36, 91, 92]. Because the parent artery is located in proximity to the skull base, the surgical access of these aneurysms is often difficult. In order to address this issue, and many others, the first flow diverter device sanctioned for use was in 2011, being designated for wide-necked intracranial aneurysms of the ICA in adults [37]. Fortunately, small aneurysms of the cavernous segment generally present a low risk of rupture [73]. Therefore, taking into consideration the hemorrhage rates described by ISUIA for aneurysms of this location, it is generally not advisable to treat asymptomatic lesions smaller than 5 mm in any way [39, 73]. Aneurysms larger than 7 mm or those that are symptomatic can be safely treated by either method with satisfactory postoperative results. Once again, endovascular procedures are less invasive, but microsurgical clipping yields a higher rate of complete occlusion [93]. Despite this, due to the hemodynamic charge of the ICA, it is possible that pulsations, differences in wall thickness, and tension may cause clip rotation [94]. Additionally, after retractors are removed, the ensuing brain shift may determine additional kinking and subsequent stenosis of the anterior choroidal artery. ICA bifurcation aneurysms are generally scarce and, as a result, underrepresented in large prospective observational studies, leading to an enigmatic natural history [93]. For aneurysms of the paraclinoid ICA or of the ophthalmic artery, it is advisable to remove the anterior clinoid process to ensure better access and proximal control. This also alleviates the risk of causing postoperative visual disturbances, which represent a common complication of ICA aneurysm management, especially for this segment [95]. Using a bone microrongeur or an ultrasonic aspirator to perform piecemeal removal of the anterior clinoid instead of a high-speed drill leads to fewer such complications [95, 96]. Small UIAs of the paraclinoid ICA that are medially pointing can also be safely approached from the contralateral side, thus diminishing the need of mobilizing the optic nerves as well as of performing anterior clinoidectomy [97]. As a remark, appropriate selection of therapeutic method for unruptured aneurysms of the ICA and its branches should factor in the individualities of the lesions themselves. Ideally, a hybrid unit would allow either approach and the possibility of converting an endovascular procedure into an open surgical intervention in the case of intraprocedural complications (**Figure 3**). Aneurysms of the posterior circulation, including the basilar artery apex or the posteroinferior cerebellar artery (PICA), have a much higher propensity to rupture [36, 73, 98]. Therefore, a conservative approach would be inadvisable for UIAs of this location. However, there is little data comparing the endovascular and surgical treatment of posterior circulation UIAs. After ISAT and the ensuing paradigm shift, there has been a scarcity of microsurgical reports on basilar apex aneurysms. Tjahjadi et al. reported a significantly higher rate of good and fair outcome (71 and 16%, respectively) after surgery of UIAs of the basilar apex than after clipping of ruptured lesions of the same site (49 and 19%, respectively) [99]. Nanda et al. also reported good outcomes following microsurgical clipping (71.9%) and asserted that a non-dominant PCoA (especially if hypoplastic) can be safely divided

in the perforator-free area as to allow additional retraction of the ICA [100]. ISUIA revealed similar clinical outcomes for the patients recruited; however, the

**158**

*Illustrative case 1. (A) Preoperative CTA of a 21-year-old male with an incidentally discovered aneurysm of the right internal carotid artery (paraclinoidal segment). Video 1 is available at: https://bit.ly/2Z8W6rm. We used a right frontolateral craniotomy and approached the aneurysm via the Sylvian fissure. We drilled the anterior clinoid process, but the aneurysm ruptured during initial attempt at clipping. Because of its sheer size, we used three fenestrated clips to occlude the aneurysmal sac. The patient was discharged with no neurological deficit. (B) MRI scan, TOF sequence, at 1-year follow-up, showing the presence of the clip and no intraluminal flow.*

endovascular procedures only achieved complete occlusion in approximately half of the cases treated [50, 101]. In contrast, aneurysms of the PICA (and to a certain extent the vertebral artery—VA) are still primarily treated via clipping due to their wide necks, generally multilobulated and nonsacular characteristic, thrombosed lumens, emerging arteries, or distal locations that render coiling substandard [102]. The lower cranial nerves encountered in the surgical field can easily and securely be avoided, especially via the transcondylar approach [103]. Moreover, cases in which microsurgery should be more fervidly supported number those with unfavorable endovascular access, very small aneurysm domes, or contraindications for stent usage (intolerance to dual antiplatelet therapy, nickel allergy, etc.) [85, 101].

The previously mentioned UCAS and ISUIA are regarded as the most prudently devised large studies vis-à-vis the natural history of UIA, with numerous guidelines having been published in their wake in order to improve management decisionmaking [78]. However, imaging control was not compulsory in ISUIA; therefore, it could not tackle the possibility of aneurysms eventually changing their morphology or size. Moreover, there is the question of the UCAS not being relevant for populations outside Japan. There are still centers that recommend treatment for all small aneurysms possessing risk of developing SAH, the presence of a daughter sack or multiple aneurysms [78, 104]. After the ISAT was published, endovascular techniques gained a boost in popularity in the USA for both ruptured and unruptured aneurysms, overtaking surgical treatment in number of procedures performed [105]. Previous analyses show that coiling was associated with fewer complications, lower mortality, faster hospital discharge, and significantly lower costs than clipping [105, 106]. However, in centers outside the USA, where hospitalization, procedure, and nursing costs are lower, the differences concerning patient expenses are smaller. In South Korea, it seems that coiling is more expensive than clipping for UIAs, and this may also be available for developing countries [106]. The principal reason for this is the cost of endovascular implantable devices themselves (stents, coils and flow diverters, etc.), constituting more than 50% of procedure-related costs [107, 108]. Even so, a previous meta-analysis concluded that coiling generated a higher independent outcome and lower mortality rate, being the more costeffective method of the two [108].

In aspects to randomized studies comparing endovascular therapy to surgery, the literature is extremely limited. The Collaborative Unruptured Endovascular Versus surgery (CURES) trial, which randomized 104 patients harboring unruptured between 3 and 25 millimeters to either coiling (*n* = 56) or clipping (*n* = 48), showed that there were no significant differences regarding in aneurysm occlusion rate, mortality, and morbidity after 1 year [80, 109]. Nevertheless, there were more patients with perioperative neurological deficit after clipping and with hospitalizations beyond 5 days. Mortality and morbidity rates for CURES were lower than reported in the ISUIA regarding both clipping and coiling [109]. Another prospective study, the trial on endovascular management of unruptured intracranial aneurysms (TEAM), which compared coiling to observational management, was halted less than 3 years after initiation as a result of poor recruitment [110].

Another controversial subject is the management of aneurysm remnant or repermeabilization after clipping or coiling. It has been repeatedly demonstrated that microsurgery leads to fewer such instances [75–82]. Although the issue of hemorrhage after initial treatment and its consequences have been extensively covered for ruptured aneurysms, there is currently no such data for UIAs [39]. Patients should therefore be regularly monitored (we recommend yearly CTA investigations), regardless of the form of treatment and any increase in size or change in morphology be contended judiciously.

Currently, the ideal strategy for solitary unruptured aneurysms is elusive. Although of great consequence, an issue seldom considered in these studies is the experience and proficiency of the neurosurgeon [73]. This is expressly observed in high-volume centers with a large number of operated cases, where outcomes are unquestionably much more favorable. Regardless, surgical prophylaxis of rupture via clipping remains a safe, effective, and possibly curative option. It remains to be seen whether the trends will continue to favor endovascular procedures or if an unexpected shift in balance might rejuvenate the popularity of surgical intervention.
