Published online before print October 30, 2008, doi: 10.1161/STROKEAHA.108.524777
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(Stroke. 2009;40:129.)
© 2009 American Heart Association, Inc.
Original Contributions |
Symptomatic and Silent Ischemia Associated With Microsurgical Clipping of Intracranial Aneurysms
Evaluation With Diffusion-Weighted MRI
From the Departments of Neurosurgery (N.K., M.O., A.F.K.) and Neuroradiology (E.E.), University of Arkansas for Medical Sciences, Little Rock, Ark.
Correspondence to Niklaus Krayenbühl, MD, Department of Neurosurgery, University Hospital Zürich, Frauenklinikstr. 10, 8091 Zürich, Switzerland. E-mail nkrayenbuehl{at}bluewin.ch
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Abstract |
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Background and Purpose— Silent ischemic events are known to occur during diagnostic and interventional endovascular procedures between 10% and 69% of the time. The occurrence of silent and symptomatic ischemic events in the surgically treated population is not known, although atherosclerotic changes of intracranial vessels or within the aneurysms wall or neck area are seen often during surgery.
Methods— Patients with unruptured and ruptured intracranial aneurysms treated by microsurgical clipping were prospectively evaluated with MRI using diffusion-weighted imaging sequences before and within 24 hours after surgery. Patients were evaluated clinically before and after surgery. During surgery, the overall and maximal time of temporary occlusion as well as the total number of temporary and finally applied clips was noted. Diffusion-weighted images were analyzed with determination and characterization of diffusion-weighted imaging abnormalities.
Results— Thirty-six patients with 51 aneurysms were included. One symptomatic and 5 silent ischemic lesions were found in 5 patients. This represents a risk of silent ischemia of 9.8% per treated aneurysm and a risk of symptomatic stroke of 2%. The most significant risk factor in increasing order was: age (P<0.05), presence of thrombus (P<0.05), number of final clips applied (P<0.05), number of temporary clips used (P<0.01), total time of temporary clip occlusion (P<0.001), and maximal time of temporary occlusion (P<0.001).
Conclusions— The risk of silent and symptomatic ischemic events during microsurgical clipping of intracranial aneurysms seems to be low. Microsurgical clipping is safe and should continue to be strongly considered as a treatment option.
Key Words: aneurysm • brain imaging • brain ischemia • neurosurgery • outcome
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Introduction |
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Silent ischemic events are known to occur during diagnostic and interventional endovascular procedures.1 However, it has become clear that silent ischemic events in the deep white matter are not really silent.2 Although the patient’s routine neurological examination may be normal, an in-depth evaluation with neuropsychological and cognitive testings is likely to reveal deficits that are otherwise not easy to detect.
The recently published results of the ISAT study3 led to a significant increase in the number of endovascular procedures performed for the treatment of intracranial aneurysms. Although the study itself included only patients with subarachnoid hemorrhage and 93% of the patients included in the study had small-sized aneurysms, endovascular coiling for aneurysms was performed for the treatment of unruptured aneurysms as well as large and complex types of aneurysms. Several previously reported studies indicate that ischemic events, both silent and symptomatic, are frequent during endovascular coiling of intracranial aneurysms and more frequently when treating more complex aneurysms, including more involved steps such as balloon-assisted remodeling.1,4–11 This fact continues to be true even after the use of anticoagulants during the procedures.5,7–11
The occurrence of silent ischemic events in patients with aneurysms treated with microsurgical clipping is not known. In addition, it is our belief that there is a good number of aneurysms that are better served with microsurgical clipping performed by an experienced cerebrovascular team. Based on this, we performed this study to analyze the risk of symptomatic and silent ischemia during the microsurgical clipping of intracranial aneurysms using MRI. To determine the individual risk factors for procedure-related ischemia, which are related to the manipulation of each individual aneurysm, we analyzed prospectively every individually clipped aneurysm in a continuous cohort of patients. We also looked at the available literature as it relates to the occurrence of ischemia during endovascular coiling of aneurysms and tried to compare and contrast the results.1,4–6,8–12
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Methods |
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All patients with ruptured and unruptured intracranial aneurysms admitted between December 2005 and March 2007 to our institution were prospectively evaluated with MRI before and within 24 hours after microsurgical clipping of the aneurysm performed by the senior author (A.F.K.). The following patients were excluded from this study: (1) patients with cerebral angiography (digital subtraction angiography) after the preoperative MRI study. This was meant to exclude those who may have developed digital subtraction angiography-related ischemic lesions; (2) patients who were not cooperative or had contraindications for MRI due to their medical condition; (3) patients in whom emergency operation did not allow MRI study before surgery (such as patients with hematomas); (4) patients in whom the aneurysm was treated with a bypass; and (5) patients presenting with clinical and/or radiological signs of vasospasm.
For radiological evaluation, we used the following MRI sequences: T1, T2, fluid-attenuated inversion recovery, diffusion, and perfusion and MR angiography. All MRI studies were evaluated by one neuroradiologist (E.E.) for detection of signs of ischemia.
In all patients, the following parameters were collected: age, sex, presence of subarachnoid hemorrhage (SAH), day after SAH, grading according to the Yasargil grading score (Table 1),13 presence of vascular risk factors like arterial hypertension, smoking habit, and history of prior cerebral ischemia. The aneurysm number, their sizes (small <7 mm, medium 7 to 12 mm, large 13 to 25 mm, giant >25 mm), and location were noted. The patients were clinically evaluated before and after surgery to detect any new neurological deficits.
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During the whole surgical procedure, patients were kept normovolemic with a mean arterial pressure between 80 and 105 mm Hg. No burst suppression was performed nor was mannitol or other medications used for brain protection during the clipping process. The microsurgical technique included either a pterional or pretemporal craniotomy with wide opening of the basal cisterns and opening of the proximal sylvian fissure and anterior sylvian fossa. This allowed quantifying the extent of atherosclerotic disease of the intracranial vessels by the view through the microscope using a grading system shown in Table 2. The presence of an intra-aneurysmal thrombus and of peri- or intra-aneurysmal atherosclerotic plaques was noted. The number of temporary clips applied was counted and the maximal and total time of temporary occlusion recorded. Also, the total number of final clips applied was counted, including all the final clips that were put, removed, or readjusted (only counted if the clip was completely opened) during the clipping process.
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Statistical analysis was performed to determine individual risk factors for procedure-related ischemia based on the number of aneurysms using the SPSS software. Ordinal variables were re-encoded numerically and patient groups were compared by univariate analysis of variance.
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Results |
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Thirty-six patients (4 male, 32 female; mean age, 54.4 years) with 51 aneurysms were included in the study. Five patients (14%) had a history of cerebrovascular ischemia, 22 (61%) were known for arterial hypertension, and 25 (69%) were smokers. According to the Yasargil grading system, 25 (69.4%) patients were classified as Grade 0, 2 (5.6%) as Grade 1, 6 (16.7%) as Grade 2, 2 (5.6%) as Grade 3, and one (2.8%) as Grade 4, meaning also that 11 patients (31%) presented with SAH. All patients with SAH were operated on within the first 48 hours after bleeding and preoperative CT angiography, MR angiography, or digital subtraction angiography did not show signs of vasospasm, which could have influenced the incidence of ischemia. The sizes of the aneurysms were as follows: small, 23 (45.1%); medium, 17 (33.3%); large, 8 (15.7%); and giant, 3 (5.9%). The distribution of the aneurysms according to their location is shown in Table 3. In 21 patients (58.3%), one aneurysm was clipped, in 5 patients (13.9%) 2 aneurysms, in 3 patients (8.3%) 3 aneurysms, and in one patient (2.8%) 5 aneurysms. The grading of atherosclerotic changes according to Table 2 was Grade 0 (39.2%), Grade 1 (39.2%), Grade 2 (9.8%), and Grade 3 (11.8%). Twenty aneurysms (39.2%) showed atherosclerotic plaques within the dome or close to the base and 6 aneurysms (11.8%) were partially thrombosed.
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Radiological Results
In 51 clipped aneurysms, 6 ischemic lesions were found in 5 patients with either large or giant aneurysms. Only one of 6 lesions was symptomatic, and 5 were silent. Three of these 5 patients had a SAH. Two patients had a basilar tip, one a partially thrombosed anterior communicating aneurysm, one a partially thrombosed superior cerebellar aneurysm, and one a large and complex middle cerebral artery bifurcation aneurysm. The distribution of the ischemic lesions was confined to the vascular territory of perforating arteries in 50% of cases, 2 of them with basilar artery and one with middle cerebral artery aneurysm. These findings represent a risk of silent ischemia of 9.8% per aneurysm and a risk of symptomatic stroke of 2%.
Statistical Analysis
Univariant analysis showed statistical significance for several parameters regarding the risk of stroke. Most significant variable in increasing order was: age (P<0.05), presence of thrombus (P<0.05), number of final clips applied (P<0.05), number of temporary clips used (P<0.01), total time of temporary clip occlusion (P<0.001), and maximal time of temporary occlusion (P<0.001). Other factors did not reach statistical significance like the size of the aneurysm (P=0.64) and the grade of atherosclerotic disease (P=0.77). Detailed analysis is shown in Table 4.
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Discussion |
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The ISAT study has created a new paradigm in the treatment of intracranial aneurysms.3 Although the study was restricted to patients who had SAH and 93% of the patients included in the study had small aneurysms, the trend in many centers is to refer every aneurysm to endovascular therapy as the primary treatment modality. In many instances, this is being done irrespective of the aneurysm location, size, dimensions, and the lack of durability of the treatment. The occurrence of ischemic events both, silent and symptomatic, during diagnostic and therapeutic endovascular procedures is not very low and cannot be ignored.1 Qureshi et al reviewed 1547 patients treated with the Guglielmi detachable coil for intracranial aneurysms and reported a risk of transient ischemic attack of 1.9% and a stroke risk of 5.6%.14 Derdeyn et al had 10 ischemic events in 9 patients in 159 Guglielmi detachable coil procedures, one of them with SAH.7 Soeda et al looked at the thromboembolic events associated with Guglielmi detachable coil embolization of asymptomatic cerebral aneurysms.11 They evaluated 66 consecutive cases with the use of diffusion-weighted MRI. Forty-nine percent of the patients were treated with a balloon-assisted technique. Diffusion-weighted images were performed in 66 patients at 2 to 5 days after embolization. Hyperintense lesions occurred in 40 patients (61%) and 16 patients (40%) had neurological deteriorations. They did mention that hyperintense lesions were more frequently seen in wide neck (73%) or large (100%) aneurysms when balloon-assisted techniques were used during the procedure and confirmed by multivariant analysis that the use of this technique resulted in a significant association with the occurrence of ischemic changes. From their study, they concluded that thromboembolic events related to Guglielmi detachable coil embolization are common and more so in wide neck and/or large aneurysms, especially when the balloon-assisted technique is used. In another study, Grunwald et al evaluated the frequency and causes of thromboembolic events associated with endovascular embolization with symptomatic aneurysms.8 They studied the occurrence of hyperintense lesions on diffusion-weighted images in 50 patients. The aneurysm sizes varied between 3 and 15 mm. New hyperintense lesions occurred in 21 of the 50 patients (42%) on diffusion-weighted imaging studies. In 33%, there was more than one lesion and in 19%, their lesions were 2 to 10 mm in size. One patient had a lesion >10 mm in size. This high rate of thromboembolic events occurred despite the use of anticoagulation with heparin. In another study by Sakai et al, they evaluated 137 patients who received 154 neurointerventional procedures and studied the diffusion-weighted images before and within 5 days after treatment.15 Diffusion-weighted imaging detected procedure-related lesions in 83 of 154 procedures (53.9%). Only 36 demonstrated no new neurological symptoms during and/or after the procedure. In 46.1%, there were no lesions. What is interesting in the study is the distribution of the ischemia suggested that ischemic events occur not only due to embolic phenomenon, but also due to hypoperfusion resulting in ischemia in watershed areas.
In view of the high rate of silent ischemia (10% to 69%) that occurs with endovascular procedures1,4–6,8–12 and the risk of symptomatic ischemia in 3.8% to 5.6%,7,14 we felt it important to evaluate the occurrence of such events in patients treated with microsurgical clipping techniques. We found no studies that tried to look into the rate of occurrence of such ischemic events based on MRI findings. Our findings with a rate of 9.8% for silent ischemia and of 2% for symptomatic stroke suggest that the occurrence of ischemia during microsurgical clipping of aneurysms is low, especially when the complexity of the treated aneurysms is taken into consideration because basilar apex aneurysms (23.5%) and paraclinoid aneurysms (19.6%) comprised 43% of the total number of aneurysms treated, also considering that 21% of the aneurysms were large or giant. However, our referral pattern may be a reflection of the future referral pattern of aneurysms in general. This is because the aneurysms being referred for microsurgical clipping are becoming more complex because they either failed attempts at their endovascular treatment or had regrown and/or recanalized after previous coiling procedures. This will lead us to conclude that if the majority of aneurysms get referred for microsurgical clipping to start with, the aneurysm mix may become less complex and lead to a lower rate of ischemia.
It has previously been suggested that the use of temporary clipping during microsurgery of aneurysms leads to ischemic events.16–21 The duration of temporary clipping was found to correlate with the increased occurrence of ischemic events.16,18,20 This is why in our practice we generally use short periods of temporary clip applications (<180 seconds). If the need arises for a longer temporary clip application time, we then rely on the electrophysiological changes that may occur during intraoperative monitoring. We routinely use intraoperative somatosensory-evoked potentials and electroencephalography. More recently, we have used motor-evoked potentials as well. Intraoperative monitoring in our experience has proven to be of significant value in guiding the temporary clip application process. We generally avoid using cerebral protection agents because of their questionable benefit and to avoid a false sense of security, which may lead to prolonging the temporary clip application time. It also interferes with the intraoperative electrophysiological monitoring.
In our statistical analysis, we found out that multiple uses of temporary clips as well as the longer period of temporary clip applications influence the occurrence of both silent and symptomatic ischemia. However, we have to keep in mind that one longer clip application influences the total occlusion time. Repeated clip applications not only of the temporary clips, but also the final clips increased the risk of ischemic changes. This may be due to the fact that a higher number of permanent clips is usually needed for more complex aneurysms that usually necessitate more surgical manipulation. This may have led to formation of new microthrombi or detachment of already existing thrombi. In our study, the presence of intra-aneurysmal thrombus increases the risk of ischemic events, a factor that should be considered in such cases. In our practice, when possible, we preoperatively start patients with suspected or confirmed an intra-aneurysmal clot or thrombus on 81-mg aspirin tablets.
The age of the patients seems to correlate with the higher occurrence of ischemic, both silent and symptomatic, events in our patients did not seem to be related to the extent of atherosclerotic disease found involving the blood vessels. This may be related to the lack of adequate collateral flow in these patients.
Our study is one of the few, if not the first, that looks at the occurrence of both silent and symptomatic ischemic events during microsurgical treatment of aneurysms based on MRI criteria. The occurrence of both symptomatic and asymptomatic ischemia during microsurgical clipping of aneurysms seems to be much less commonly encountered than what has been reported for endovascular procedures despite the later taking advantage of full anticoagulation. These findings and the better durability achieved of microsurgical clipping of aneurysms should be factored into the decision-making process of what would be the best treatment option for a particular aneurysm.
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Conclusion |
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TopAbstractIntroductionMethodsResultsDiscussionConclusionReferences |
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The risk of silent and symptomatic ischemic events during microsurgical clipping of intracranial aneurysms seems to be low, especially in view of the higher complexity of aneurysms in our cohort. The risk of ischemia tends to increase with the increase in aneurysm complexity, especially in partially thrombosed aneurysms. Microsurgical clipping of intracranial aneurysms is safe, durable, and should continue to be strongly considered as a treatment option.
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Acknowledgments |
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Disclosures
None.
Received May 2, 2008; accepted May 27, 2008.
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References |
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