Subtle structural change demonstrated on T2-weighted images after clipping of unruptured intracranial aneurysm: negative effects on cognitive performance

Clinical article

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Object

The mechanisms underlying neurocognitive changes after surgical clipping of unruptured intracranial aneurysms (UIAs) are poorly understood. The aim of this study was to investigate factors that determine postoperative cognitive decline after UIA surgery.

Methods

Data from 109 patients who underwent surgical clipping of a UIA were retrospectively evaluated. These patients underwent neuropsychological examinations (NPEs), including assessment by the Wechsler Adult Intelligence Scale-Third Edition and the Wechsler Memory Scale-Revised before and 6 months after surgical clipping of the UIA. Results of NPEs were converted into z scores, from which pre- and postoperative cognitive composite scores (CSpre and CSpost) were obtained. The association between the change in CS between pre- and postoperative NPEs (that is, CSpost − CSpre [CSpost − pre]) and various variables was assessed. These latter variables included surgical approach (anterior interhemispheric approach or other approach), structural change evidenced on T2-weighted imaging at 6 months, somatosensory evoked potential amplitude decrease greater than 50% during aneurysm manipulation, preexisting multiple ischemic lesions in the lacunar region detected on preoperative T2-weighted imaging, and total microsurgical time. Paired t-tests of the NPE scores were performed to determine the net effect of these factors on neurocognitive function at 6 months.

Results

A significant CSpost − pre decrease was observed in patients with a structural change on postoperative T2-weighted imaging when compared with those without such a change on postoperative T2-weighted imaging (−0.181 vs 0.043, p = 0.012). Multiple regression analysis demonstrated that postoperative T2-weighted imaging change independently and negatively correlated with CSpost − pre (p = 0.0005). In group-rate analysis, postoperative NPE scores were significantly improved relative to preoperative scores.

Conclusions

Minimal structural damage visualized on T2-weighted images at 6 months as a result of factors such as pial/microvascular injury and excessive retraction during surgical manipulation could cause subtle but significant negative effects on postoperative neurocognitive function after surgical clipping of a UIA. However, this detrimental effect was small, and based on the group-rate analysis, the authors conclude that successful and meticulous surgical clipping of a UIA does not adversely affect postoperative cognitive function.

Abbreviations used in this paper:ACoA = anterior communicating artery; CS = composite score; IQR = interquartile range; MCA = middle cerebral artery; mRS = modified Rankin Scale; NPE = neuropsychological examination; PIQ = performance IQ; SSEP = somatosensory evoked potential; UIA = unruptured intracranial aneurysm; VIQ = verbal IQ; WAIS-III = Wechsler Adult Intelligence Scale-Third Edition; WMS-R = Wechsler Memory Scale-Revised.

Abstract

Object

The mechanisms underlying neurocognitive changes after surgical clipping of unruptured intracranial aneurysms (UIAs) are poorly understood. The aim of this study was to investigate factors that determine postoperative cognitive decline after UIA surgery.

Methods

Data from 109 patients who underwent surgical clipping of a UIA were retrospectively evaluated. These patients underwent neuropsychological examinations (NPEs), including assessment by the Wechsler Adult Intelligence Scale-Third Edition and the Wechsler Memory Scale-Revised before and 6 months after surgical clipping of the UIA. Results of NPEs were converted into z scores, from which pre- and postoperative cognitive composite scores (CSpre and CSpost) were obtained. The association between the change in CS between pre- and postoperative NPEs (that is, CSpost − CSpre [CSpost − pre]) and various variables was assessed. These latter variables included surgical approach (anterior interhemispheric approach or other approach), structural change evidenced on T2-weighted imaging at 6 months, somatosensory evoked potential amplitude decrease greater than 50% during aneurysm manipulation, preexisting multiple ischemic lesions in the lacunar region detected on preoperative T2-weighted imaging, and total microsurgical time. Paired t-tests of the NPE scores were performed to determine the net effect of these factors on neurocognitive function at 6 months.

Results

A significant CSpost − pre decrease was observed in patients with a structural change on postoperative T2-weighted imaging when compared with those without such a change on postoperative T2-weighted imaging (−0.181 vs 0.043, p = 0.012). Multiple regression analysis demonstrated that postoperative T2-weighted imaging change independently and negatively correlated with CSpost − pre (p = 0.0005). In group-rate analysis, postoperative NPE scores were significantly improved relative to preoperative scores.

Conclusions

Minimal structural damage visualized on T2-weighted images at 6 months as a result of factors such as pial/microvascular injury and excessive retraction during surgical manipulation could cause subtle but significant negative effects on postoperative neurocognitive function after surgical clipping of a UIA. However, this detrimental effect was small, and based on the group-rate analysis, the authors conclude that successful and meticulous surgical clipping of a UIA does not adversely affect postoperative cognitive function.

Indications for the treatment of unruptured intracranial aneurysms (UIAs) remain controversial, mostly because the overall surgical morbidity and mortality rates of this condition range from 1% to 15%.6,13,15,17,24,25 To justify treatment, surgical risks need to be weighed against the risks of conservative management.

Unruptured intracranial aneurysms can be treated with surgical clipping or endovascular coiling. The advantage of surgical clipping is that it can exclude the aneurysm completely from the circulation by placing the clip across the neck, thereby ensuring long-term durability of the treatment.21 By contrast, coil embolization is less invasive. Thus, in addition to the usual primary outcomes of morbidity and mortality, subtle complications, such as subclinical neurocognitive decline, should be considered. Indeed, the International Study of Unruptured Intracranial Aneurysms (ISUIA) suggested that the high postsurgical morbidity experienced by these patients was largely attributable to impaired cognitive status.24

When performing surgical clipping of UIAs through the pterional approach, cerebral blood flow in the ipsilateral perisylvian area was reduced by 10%–15% in the acute postoperative period due to surgical manipulation.19 Some reports have suggested that there is a higher incidence of neuropsychological deterioration after surgery for anterior communicating artery (ACoA) aneurysms and/or when the interhemispheric approach was used.8,14 In contrast, others have demonstrated that successful surgical treatment of UIAs does not impair cognitive function.9,15,16,22 These conflicting results are likely due to differences in methodological factors.

The possible detrimental effects related to surgical manipulation include direct pial and microvascular injury during fissure dissection, ischemia caused by temporary vessel occlusion, and mechanical/ischemic damage caused by brain retraction. The adverse effect of prolonged general anesthesia and surgical manipulation might be attenuated via a “slow and steady” meticulous manipulation approach.

The goal of this study was to investigate the relationship between postoperative cognitive decline after UIA surgery and clinical variables such as 1) applied surgical approach route, with the assumption that the anterior interhemispheric approach might cause a negative effect on cognition relative to other approaches, such as the pterional approach; 2) structural damage to the brain parenchyma as assessed by T2-weighted imaging at 6 months when compared with preoperative imaging; 3) temporary ischemia detected by somatosensory evoked potential (SSEP) amplitude decrease; 4) surgical invasiveness quantified by surgical/microsurgical time and/or clipping of multiple aneurysms; and 5) a preexisting patient condition, such as advanced age and/or multiple ischemic lesions in the lacunar region. This study also investigated whether successful UIA surgery affects neurocognitive function at 6 months.

Methods

This retrospective study was approved by the institutional review board at Fuji Brain Institute and Hospital, and all individuals provided informed consent before participating in the study. We reviewed 109 consecutive patients who underwent UIA surgery between November 2007 and December 2012 and who satisfied the following inclusion criteria: 1) completion of preoperative (within 1 week preoperatively) and postoperative (approximately 6 months or later) neuropsychological examinations (NPEs), including the Wechsler Adult Intelligence Scale-Third Edition2 (WAIS-III) and the Wechsler Memory Scale-Revised20 (WMS-R); and 2) no major permanent postoperative focal neurological deficit caused by surgery (modified Rankin scale [mRS] Score 0 or 1).

Surgical treatment is usually considered for aneurysms that are 5 mm or larger. However, surgery might be considered for aneurysms smaller than 5 mm when the risk of rupture is estimated to be high due to location or irregular shape. The surgical risk was explained to the patients based on a surgical mortality rate of less than 1% and a surgical morbidity rate of less than 3% at our institution from October 2006 to October 2007. However, the details of the explanation of morbidity were modified depending on the location of the aneurysm. For example, hemiparesis was emphasized as a risk for patients undergoing surgical treatment for a middle cerebral artery (MCA) aneurysm (because of the potential for injury to the lenticulostriate artery), while memory disturbance was emphasized as a risk for those with ACoA aneurysms (because of the potential for injury to the hypothalamic perforator). All patients underwent preoperative NPEs after receiving these explanations.

A standard pterional approach using an operative microscope was performed after widely opening the sylvian fissure. For all ACoA aneurysms without concomitant MCA or internal carotid artery aneurysms, the anterior interhemispheric approach7 was used. In several other cases, the distal interhemispheric approach for distal anterior cerebral artery aneurysms, the subtemporal approach for aneurysms at the bifurcation between the basilar artery and anterior inferior cerebellar artery, and the suboccipital approach for a vertebral artery aneurysm were performed. All operations were performed or supervised by the first author (T.I.).

Demographics, clinical information, MRI, CT scanning, digital subtraction angiography, SSEP, NPE, and follow-up data were analyzed. Aneurysm size was measured by maximum diameter using 3D volume rendering derived from MR angiography. When a patient had multiple aneurysms, the size and location of the largest aneurysm or the size and location of the aneurysm that was regarded as the most difficult to manage were registered (for example, if a patient had a 5-mm basilar tip aneurysm and an 8-mm MCA aneurysm that had been treated in one pterional approach, we registered 5 mm for the aneurysm size and the basilar artery as the aneurysm location). When patients had multiple aneurysms of equal size at different vascular sites and the technical difficulty was regarded as similar, the aneurysm location was registered as multiple.

In the pterional approach, SSEP responses were monitored from the contralateral median nerve stimulation at the wrist. Likewise, SSEP responses were monitored from the bilateral posterior tibial nerves when the interhemispheric approach was used and from all 4 extremities when clipping of vertebrobasilar aneurysms was performed. We defined a considerable degree of ischemic impact as an SSEP amplitude decrease more than 50% when compared with steady state control value.23 The SSEP results were dichotomized according to whether any SSEP amplitude decrease greater than 50% was observed during temporary vessel occlusion/aneurysm manipulation.

To determine the long-term structural damage, T2-weighted MRI was performed at 6 months, and the images were compared with images obtained preoperatively. Imaging was performed using a 1.5-T MRI system (slice thickness 6 mm, TR 3800 msec, TE 96 msec, matrix 448 × 392; Symphony Advance, Siemens). Any visible changes, such as slight perifocal atrophy related to surgical manipulation (other than the artifact made by the clip itself), were prospectively documented on the medical record and retrospectively reviewed, and the results were dichotomized as to whether any T2-weighted imaging change had occurred. On preoperative T2-weighted imaging, preexisting multiple ischemic lesions in the lacunar region were also assessed as representative of previous ischemic cerebrovascular disease.

Neuropsychological examination was performed using the Japanese versions of the WAIS-III and WMSR.2,20 Neuropsychological examinations were assessed and recorded prospectively by speech therapists or by psychotherapists who were experienced in conducting NPEs. These evaluators were aware of the fact that patients had undergone UIA surgery but were blinded to detailed clinical variables. From the WAIS-III, verbal IQ (VIQ) and performance IQ (PIQ) were obtained. From the WMS-R, the composite memory score (WMS-memory) and attention/concentration score (WMS-attention) were obtained. Preoperative NPEs were performed within 1 week before UIA surgery. Postoperative NPEs were performed approximately 6 months after UIA surgery (median 6 months, interquartile range [IQR] 6–7 months). In 5 patients, bilateral craniotomies for clipping of UIAs were performed in 2 separate operations. In those patients, postoperative NPEs were performed approximately 6 months after the second aneurysm surgery.

The first step in generating the overall cognitive composite score (CS) was to transform the 4 scores (VIQ, PIQ, WMS-memory, and WMS-attention) of each patient into a z score as follows: z score = (x − m)/SD, where x = the score for the test, m = mean score of the test for the entire cohort, and SD = the standard deviation of the score for the entire cohort. The z scores of each test were then summed and divided by the total number of tests to calculate the patient's CS so that CS = Σz scores/n, where n = total number of tests performed in the patient.3,10 After obtaining the preoperative CS (CSpre) and the postoperative CS (CSpost), overall cognitive change was measured by calculating the change in CS so that CSpost − pre = CSpost − CSpre.

The primary aim of this study was to investigate the change in the cognitive composite score (CSpost − pre) according to specific clinical variables. These variables included patient age, sex, aneurysm location and surgical approach, comorbidity, aneurysm size, structural change observed on postoperative T2-weighted imaging, SSEP amplitude decrease greater than 50%, postoperative event between pre- and post-NPE (postoperative event), multiple clipping for multiple aneurysms, preexisting multiple lacunar ischemia noted on T2-weighted MRI, and total surgical/microsurgical time (both dichotomized by median value [284 minutes for surgical time and 155 minutes for microsurgical time] in univariate analysis).

Univariate analysis was performed between CSpost − pre and the clinical variables. The t-test or ANOVA was used to examine the differences in CSpost − pre stratified according to the clinical variables. A stepwise multiple regression analysis was performed to select the factors predicting the CSpost − pre and to determine the independent effects of selected predictors. To analyze complex variables, aneurysm location and surgical approach were dichotomized into the utilization of the anterior interhemispheric approach or other approach, and aneurysm size was dichotomized into > 5 mm versus ≤ 5 mm. The inclusion and exclusion criteria for the stepwise method were both set at < 0.20 to include more variables in the final model.

The secondary aim of this study was to determine the net result of various factors associated with successful UIA surgery on neurocognitive function at 6 months after surgery in the group-rate analysis. This was examined using paired t-tests to analyze the difference in the 4 NPE scores (VIQ, PIQ, WMS-memory, and WMS-attention).

Two-sided probability values < 0.05 were considered to represent statistical significance. Statistical analysis was performed using the Statistical Analysis System (SAS Institute, Inc.).

Results

A total of 128 patients underwent both surgical clipping of the UIA and preoperative NPE between November 2007 and December 2012 at Fuji Brain Institute and Hospital. Of these, 11 patients were excluded because they were lost to follow-up even though they completed a preoperative NPE and had an uneventful postoperative course. Three patients were excluded because they developed postoperative neurological deficit (one with left hemiparesis due to perforator injury during surgery, one with sensory aphagia due to cardiac embolic stroke on postoperative Day 10, and one with generalized convulsions at 4 months postoperatively) that prevented postoperative NPE assessment, although all of these patients regained an mRS score of 0 or 1 by 1 year after surgery. One patient was excluded because he refused to undergo WAIS-III assessment and completed only preoperative and postoperative WMS-R assessment. Another 4 patients were excluded because only the WAIS-III assessment was performed as the preoperative and postoperative NPE.

Thus, a total of 109 patients completed NPEs before and after UIA aneurysm surgery (Table 1). Acute injury caused by surgical manipulation, indicated by such signs as retraction effect (hypodensity suggestive of edema), slight contusion, and subdural hematoma near the surgical field, was revealed in 11 patients according to CT scanning performed during the first 2 weeks postoperatively, but CT scanning did not show a space-occupying hematoma or lobar infarction. Therefore, none of the patients suffered from permanent neurological deficits that influenced the final mRS score. Preoperative T2-weighted imaging was performed approximately 5 days before surgery (median 5 days, IQR 3–6 days), and postoperative T2-weighted imaging was performed approximately 6 months after surgery (median 6 months, IQR 6–7 months). Postoperative T2-weighted imaging changes were demonstrated in 14 patients, in whom the most frequent structural change was slight widening of the inferior horn of the lateral ventricle, suggestive of focal brain atrophy due to surgical invasion on the side of pterional approach (12 patients), followed by a frontal white matter lesion in the anterior interhemispheric approach (1 patient), and slight cerebellar atrophy after the suboccipital approach (1 patient). Complete clipping was confirmed by postoperative digital subtraction angiography at around 8 days after surgery (median 8 days, IQR 7–9.5 days) in all but one patient who underwent successful ACoA aneurysm clipping but had suboptimal renal function. Somatosensory evoked potential amplitude decrease greater than 50% was observed in 7 patients. A temporary clip was used in 60 patients. In 11 patients, postoperative events (for example, transient ischemic attack, temporary focal neurological deficit due to postoperative subdural hematoma in the surgical field, breast cancer surgery, forearm fracture, and chronic subdural hematoma) occurred without serious permanent postoperative neurological deficits in any patient. In 14 patients, multiple clipping for multiple aneurysms was performed, including in 7 patients through 1 craniotomy, in 5 patients by bilateral craniotomy during 2 separate operations, and in 2 patients by 2 separate craniotomies in 1 operation. Preexisting multiple ischemic lesions in the lacunar region, as verified on preoperative T2-weighted imaging to represent previous ischemic cerebrovascular disease, was confirmed in 41 patients. The mean total operative time was 300 ± 89 minutes, and the mean microsurgical manipulation time was 164 ± 63 minutes.

TABLE 1:

Patient characteristics and variables*

FactorValue
mean age in yrs62 ± 10
female sex75 (69)
aneurysm location
 ICA36 (33)
 MCA36 (33)
 ACoA19 (17)
 distal ACA4 (4)
 BA7 (6)
 VA3 (3)
 multiple4 (4)
surgical approach
 anterior interhemispheric19 (17)
 distal interhemispheric4 (4)
 rt pterional40 (37)
 lt pterional36 (33)
 lt subtemporal1 (1)
 suboccipital3 (3)
 multiple approach6 (5)
hypertension106 (97)
diabetes17 (16)
hyperlipidemia60 (55)
atrial fibrillation5 (5)
smoking history34 (31)
mean aneurysm size in mm6.1 ± 2.6
postop T2WI change14 (13)
SSEP amplitude decline >507 (6)
postop event§11 (10)
multiple clippings14 (13)
preexisting multiple lacunar lesions**41 (38)
mean surgical time in mins300 ± 89
mean microsurgical time in mins164 ± 63

Values are number of patients (%) unless otherwise stated. Mean values are presented as the mean ± SD. ACA = anterior cerebral artery; BA = basilar artery; ICA = internal cerebral artery; T2WI = T2-weighted imaging; VA = vertebral artery.

Structural change as demonstrated on postoperative T2-weighted images at 6 months compared with preoperative T2-weighted images.

During temporary clipping or aneurysm manipulation.

Between pre- and postoperative NPE.

Multiple clipping for multiple aneurysms with or without multiple craniotomies.

Preexising multiple ischemic lesions in the lacunar region as verified on preoperative T2-weighted imaging.

As shown in Table 2, a significant CSpost − pre decrease was observed in patients with postoperative T2-weighted imaging changes when compared with those without postoperative T2-weighted imaging changes (−0.181 vs 0.043; p = 0.012). A stepwise multiple regression model predicting CSpost − pre was performed. After controlling for hypertension, diabetes mellitus, hyperlipidemia, aneurysm size, and SSEP amplitude decrease greater than 50%, the presence of postoperative T2-weighted imaging lesions was identified as an independent predictor of a decrease in CSpost − pre (p = 0.0005; Table 3). Somatosensory evoked potential amplitude decrease greater than 50% was also independently associated with an increase in CSpost − pre (p = 0.0039). Aneurysm size > 5 mm was nearly significantly associated with a decrease in CSpost − pre (p = 0.0562).

TABLE 2:

Univariate analysis of the relationship between change in CS and clinical variables

FactorNo. of PatientsCSpost − prep Value
MeanSD
age (yrs)0.893
 <65620.0180.332
 ≥65470.0100.294
sex0.606
 male34−0.0090.279
 female750.0250.331
aneurysm location0.989
 ICA360.0080.320
 MCA360.0150.279
 ACoA190.0540.385
 distal ACA40.0140.460
 BA7−0.0520.298
 VA3−0.0710.330
 multiple40.0620.275
approach side0.396
 rt430.0450.275
 lt38−0.0140.303
 interhemispheric230.0470.388
 bilat5−0.1870.357
hypertension0.722
 yes1060.0180.310
 no3−0.1100.539
diabetes0.349
 yes17−0.0520.365
 no920.0260.305
hyperlipidemia0.212
 yes60−0.0200.289
 no490.0560.342
atrial fibrillation0.608
 yes5−0.0570.353
 no1040.0180.314
smoking history0.484
 yes34−0.0140.251
 no750.0270.341
aneurysm size (mm)0.059
 ≤5620.0490.298
 6–1040−0.0700.317
 ≥1170.1820.357
postop T2WI change*0.012
 yes14−0.1810.333
 no950.0430.303
SSEP amplitude decline >50%0.248
 yes70.1480.254
 no1020.0050.317
postop event§0.314
 yes11−0.1040.402
 no980.0280.303
multiple clippings0.164
 yes14−0.0950.330
 no950.0300.311
preexisting multiple lacunar lesions**0.498
 yes41−0.0120.343
 no680.0300.298
surgical time (mins)0.111
 <284540.0630.336
 ≥28455−0.0330.288
microsurgical time (mins)0.501
 <155540.0350.302
 ≥15555−0.0060.328

Structural change as demonstrated on postoperative T2-weighted images at 6 months compared with preoperative T2-weighted images.

p < 0.05.

During temporary clipping or aneurysm manipulation.

Between pre- and postoperative NPE.

Multiple clipping for multiple aneurysms with or without multiple craniotomies.

Preexising multiple ischemic lesions in the lacunar region as verified on preoperative T2-weighted imaging.

TABLE 3:

Multiple regression analysis of potential predictors of change in CS

FactorCoefficientStandard Errorp Value
hypertension0.267500.177230.1343
diabetes−0.118350.080990.1470
hyperlipidemia−0.091600.059280.1254
aneurysm >5 mm−0.114290.059170.0562
postop T2WI change*−0.326020.090680.0005
SSEP amplitude decline >50%0.373530.126550.0039

Structural change as demonstrated on postoperative T2-weighted images at 6 months compared with preoperative T2-weighted images.

p < 0.05.

During temporary clipping or aneurysm manipulation.

In the group-rate analysis, postoperative NPE scores (VIQ, PIQ, WMS-memory, and WMS-attention) were significantly improved relative to preoperative NPE scores (p = 0.0003 in VIQ, p < 0.0001 in PIQ and WMS-memory, p = 0.0391 in WMS-attention; Table 4).

TABLE 4:

Results of group-rate analysis of preoperative and postoperative neuropsychological examinations

TestMean ± SDp Value
Preop ScorePostop Score
WAIS-III, VIQ96.1 ± 14.098.1 ± 13.80.0003*
WAIS-III, PIQ97.2 ± 15.7101.5 ± 16.5<0.0001*
WMS-memory95.6 ± 14.3101.3 ± 13.9<0.0001*
WMS-attention102.0 ± 14.6103.8 ± 14.70.0391*

p < 0.05.

Discussion

Subtle Structural Change Demonstrated by T2-Weighted Imaging Associated With a Decline in Neurocognitive Function at 6 Months

The present study demonstrated that minimal structural damage, as visualized by T2-weighted imaging at 6 months after surgery, was related to a subtle but statistically significant decline in postoperative neurocognitive function. The most frequent structural change was a slight widening of the inferior horn of the lateral ventricle on the side of the pterional approach, representing some pial/microvascular injury or excessive retraction during surgical manipulation of the UIA. The extent of injury caused by brain retraction depends on the pressure exerted by the retractor, the geometry of the retractor, and the duration of retraction.11 By contrast, the specific approach (investigating the presumption that the anterior interhemispheric approach with possible bilateral medial frontal lobe damage might cause a more detrimental effect than the pterional approach), multiple approaches and/or multiple aneurysms, as well as longer operative time, were not significantly related to changes in neurocognitive function. We speculate that the final substantial structural damage, rather than the nature of approach or the length of surgery, is the prime determinant of long-term cognitive decline. Thus, we believe that every effort should be made to avoid injury to the surrounding brain tissue when performing surgical manipulation during clipping of a UIA.

Relationship Between Decrease in SSEP Amplitude During Surgery and Postoperative Neurocognitive Function

Intraoperative transient ischemia tends to cause neuronal injury and can therefore have a detrimental effect on postoperative neurocognitive function. However, the effect of temporary ischemia depends on its degree and duration. In the present study, we defined a considerable degree of ischemic impact as an SSEP amplitude decrease greater than 50% when compared with steady state control values.23 As soon as we noted a decrease in SSEP amplitude, we removed the temporary clip, repositioned the permanent clip, and/or replaced the retraction to minimize the duration of ischemia. Thus, the duration of SSEP amplitude decrease greater than 50% was quite short. Contrary to general expectation, in the present study, multivariate analysis showed that an SSEP amplitude decrease greater than 50% positively affected postoperative neurocognitive function. This might be because in cases with SSEP amplitude decrease greater than 50%, more meticulous and cautious maneuvers had been used during surgery. Further study to determine whether a longer duration of SSEP amplitude decrease greater than 50% has a detrimental effect on postoperative neurocognitive function would be of benefit.

Influence of Operative Time on Neurocognitive Function

Previous studies suggest that coil embolization may be superior to surgery in selected patients in terms of cognitive outcomes.1,18 This might be due to longer surgical times when comparing UIA surgery with coiling. However, even with the relatively long surgical time in the present study, the net NPE scores were significantly increased when compared with preoperative scores. In a residency training program in our hospital, one department chief surgeon (T.I.) and several residents performed UIA surgery in conjunction with extensive microsurgical training.4,5 Although all intraoperative decisions were made at the discretion of the first author (T.I.), most craniotomies and microsurgical fissure dissections were also performed by senior residents under supervision. This is the main reason for the relatively long operative and microsurgical times in the present study. The present study demonstrated that when surgical manipulation was performed meticulously without causing permanent structural damage to the brain, the operative time did not influence the neurocognitive result. This finding is especially relevant to the goal of maintaining the quality of UIA surgery when training young vascular neurosurgeons.

Relationship Between the Interhemispheric Approach for ACoA Aneurysms and Neurocognitive Function

There are 2 different approaches for the management of ACoA aneurysms. For example, the interhemispheric approach can damage the medial side of the bilateral frontal lobes, leading to deterioration of neuropsychological function.14 In contrast, the pterional approach might be related to excessive frontobasal retraction in conjunction with rectal gyrus aspiration to visualize complex ACoA aneurysms, eventually causing neuropsychological deterioration.8,14 In a neuropsychological substudy of the International Subarachnoid Aneurysm Trial (ISAT), cognitive impairment at 12 months was more frequent in the neurosurgery group than in the endovascular coiling group. The trial cohort comprised patients with predominantly anterior circulation aneurysms, especially ACoA aneurysms. The trial investigators suggested that frontal lobe retraction and possible gyrus rectus dissection to enable surgical clipping might have adversely affected cognition, including verbal memory, processing speed, and executive skills, in the neurosurgery group.18 Another study with ACoA aneurysms showed similar results.1 In the present study, the anterior interhemispheric approach was exclusively used in 19 patients with ACoA aneurysms, and every effort was made to avoid damage to the medial side of the bilateral frontal lobes. Contrary to findings from previous studies, the patients with ACoA aneurysms in the present study did not show reduced neurocognitive function when compared with patients with aneurysms in other locations. Thus, we believe that the anterior interhemispheric approach for ACoA aneurysms does not adversely affect neurocognitive function, as long as surgical manipulation is meticulously performed using sharp dissection under high magnification. Studies of the natural course of unruptured cerebral aneurysms in a Japanese cohort have demonstrated that small aneurysms of the ACoA were associated with a relatively high risk of rupture.12 Thus, considering that the interhemispheric approach might have an advantage from the standpoint of a wide operative field and therefore multiple options for clipping trajectory, especially when dealing with superiorly and posteriorly projected small ACoA aneurysms, we should continue to investigate the relationship between the anterior interhemispheric approach and neurocognitive function.

Effect of Age, Aneurysm Size, and Preexisting Multiple Lacunar Infarctions on Postoperative Neurocognitive Dysfunction

Variables that predict poor surgical outcome in UIA surgery include older age, larger aneurysm size (> 12 mm), and previous ischemic cerebrovascular disease.24 In the present study, aneurysm size larger than 5 mm was nearly a significant predictor of neurocognitive decline within multivariate analysis (coefficient −0.11429, p = 0.0562). The average aneurysm size was 6.2 mm in this study; not many aneurysms were larger than 12 mm. Inclusion of larger aneurysms in the study cohort might have increased the statistical power. It would be reasonable to suggest that overall surgical morbidity and mortality could increase in older patients and in those with preexisting multiple ischemic lesions in the lacunar region. However, these conditions did not affect postoperative neurocognitive function, which suggests that meticulous brain manipulation with the goal of avoiding structural damage could result in good preservation of neurocognitive function, even in this high-risk population.

Group-Rate Analysis of NPEs

The present study demonstrated that postoperative NPE scores were significantly higher than preoperative NPE scores, according to group-rate analysis. This difference could result from the practice effect, although we performed reexamination well beyond the 3-month interval in which the practice effect persists.15 Another possible factor is that treatment of the UIA alleviates the patients' stress of having a possible life-threatening lesion,9,13 thus making patients perform better after knowing that obliteration of the aneurysm was successfully performed without any obvious permanent neurological deficit.

Study Limitations

This study has several limitations. First, this was a retrospective analysis that carries the usual inherent limitations associated with this sort of study design. Second, this was a study of a relatively small number of patients. Additional cases are required to definitively determine the impact of surgical treatment of UIA on cognition.

Conclusions

Minimal structural damage, as visualized by T2-weighted imaging, at 6 months resulting from surgical manipulation (for example, pial/microvascular injury and brain retraction) can cause subtle but significant adverse effects on postoperative neurocognitive function after surgical clipping of UIAs. We speculate that cognitive decline is related to intraoperative damage to the brain rather than to the operative time or specific surgical approach. However, this detrimental effect was small, and various factors contribute. Based on the group-rate analysis, we conclude that meticulous surgical manipulation can minimize changes in cognitive function after surgical clipping of UIAs.

Disclosure

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author contributions to the study and manuscript preparation include the following. Conception and design: Inoue, Ohwaki, Tamura, Tsutsumi. Acquisition of data: Inoue. Analysis and interpretation of data: Inoue, Ohwaki, Tamura, Tsutsumi. Drafting the article: Inoue. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Inoue. Statistical analysis: Inoue, Ohwaki. Study supervision: Tamura, I Saito, N Saito.

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    Inoue TTsutsumi KAdachi STanaka SSaito KKunii N: Effectiveness of suturing training with 10-0 nylon under fixed and maximum magnification (x 20) using desk type microscope. Surg Neurol 66:1831872006

  • 5

    Inoue TTsutsumi KSaito KAdachi STanaka SKunii N: Training of A3-A3 side-to-side anastomosis in a deep corridor using a box with 6.5-cm depth: technical note. Surg Neurol 66:6386412006

  • 6

    International Study of Unruptured Intracranial Aneurysms Investigators: Unruptured intracranial aneurysms—risk of rupture and risks of surgical intervention. N Engl J Med 339:172517331998. (Erratum in N Engl J Med 340: 744 1999)

  • 7

    Ito Z: The microsurgical anterior interhemispheric approach suitably applied to ruptured aneurysms of the anterior communicating artery in the acute stage. Acta Neurochir (Wien) 63:85991982

  • 8

    Kobayashi MTakayama HSuga SOkazaki AMihara B: [Changes in proton magnetic resonance spectroscopy and Wechsler adult intelligence scale revised after clipping of unruptured aneurysms.]. No Shinkei Geka 28:6916982000. (Jpn)

  • 9

    Kubo YOgasawara KKashimura HOtawara YKakino SSugawara A: Cognitive function and anxiety before and after surgery for asymptomatic unruptured intracranial aneurysms in elderly patients. World Neurosurg 73:3503532010

  • 10

    Lal BKYounes MCruz GKapadia IJamil ZPappas PJ: Cognitive changes after surgery vs stenting for carotid artery stenosis. J Vasc Surg 54:6916982011

  • 11

    Little ASLiu SBeeman SSankar TPreul MCHu LS: Brain retraction and thickness of cerebral neocortex: an automated technique for detecting retraction-induced anatomic changes using magnetic resonance imaging. Neurosurgery 67:3 Suppl Operativeons277ons2822010

  • 12

    Morita AKirino THashi KAoki NFukuhara SHashimoto N: The natural course of unruptured cerebral aneurysms in a Japanese cohort. N Engl J Med 366:247424822012

  • 13

    Moroi JHadeishi HSuzuki AYasui N: Morbidity and mortality from surgical treatment of unruptured cerebral aneurysms at Research Institute for Brain and Blood Vessels-Akita. Neurosurgery 56:2242312005

  • 14

    Ohue SOka YKumon YOhta SSakaki SHatakeyama T: Importance of neuropsychological evaluation after surgery in patients with unruptured cerebral aneurysms. Surg Neurol 59:2692762003

  • 15

    Otawara YOgasawara KOgawa AYamadate K: Cognitive function before and after surgery in patients with unruptured intracranial aneurysm. Stroke 36:1421432005

  • 16

    Pereira-Filho AAPereira AGFaria MBLima LCSPortuguez MWKraemer JL: Microsurgical clipping in forty patients with unruptured anterior cerebral circulation aneurysms: an investigation into cognitive outcome. Arq Neuropsiquiatr 68:7707742010

  • 17

    Raaymakers TWMRinkel GJELimburg MAlgra A: Mortality and morbidity of surgery for unruptured intracranial aneurysms: a meta-analysis. Stroke 29:153115381998

  • 18

    Scott RBEccles FMolyneux AJKerr RSCRothwell PMCarpenter K: Improved cognitive outcomes with endovascular coiling of ruptured intracranial aneurysms: neuropsychological outcomes from the International Subarachnoid Aneurysm Trial (ISAT). Stroke 41:174317472010

  • 19

    Shimizu HInoue TFujimura MSaito ATominaga T: Cerebral blood flow after surgery for unruptured cerebral aneurysms: effects of surgical manipulation and irrigation fluid. Neurosurgery 69:6776882011

  • 20

    Sugishita M: [Japanese Wechsler Memory Scale-Revised.] TokyoNihon Bunka Kagakusha2001. (Jpn)

  • 21

    Tsutsumi KUeki KUsui MKwak SKirino T: Risk of subarachnoid hemorrhage after surgical treatment of unruptured cerebral aneurysms. Stroke 30:118111841999

  • 22

    Tuffiash ETamargo RJHillis AE: Craniotomy for treatment of unruptured aneurysms is not associated with long-term cognitive dysfunction. Stroke 34:219521992003

  • 23

    Wicks RTPradilla GRaza SMHadelsberg UCoon ALHuang J: Impact of changes in intraoperative somatosensory evoked potentials on stroke rates after clipping of intracranial aneurysms. Neurosurgery 70:111411242012

  • 24

    Wiebers DOWhisnant JPHuston J IIIMeissner IBrown RD JrPiepgras DG: Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 362:1031102003

  • 25

    Yamashiro SNishi TKoga KGoto TMuta DKuratsu J: Postoperative quality of life of patients treated for asymptomatic unruptured intracranial aneurysms. J Neurosurg 107:108610912007

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Article Information

Address correspondence to: Tomohiro Inoue, M.D., Department of Neurosurgery, Fuji Brain Institute and Hospital, 270-12 Sugita, Fujinomiya-shi, Shizuoka 418-0021, Japan. email: t.inoue-fujinsu@beige.plala.or.jp.

Please include this information when citing this paper: published online January 31, 2014; DOI: 10.3171/2013.12.JNS131790.

© AANS, except where prohibited by US copyright law.

Headings

References

1

Fontanella MPerozzo PUrsone RGarbossa DBergui M: Neuropsychological assessment after microsurgical clipping or endovascular treatment for anterior communicating artery aneurysm. Acta Neurochir (Wien) 145:8678722003

2

Fujita KMaekawa HDairoku HYamanaka K: Japanese Wechsler Adult Intelligence Scale ed 3TokyoNihon Bunka Kagakusha2006. (Jpn)

3

Inoue TOhwaki KTamura ATsutsumi KSaito ISaito N: Subclinical ischemia verified by somatosensory evoked potential amplitude reduction during carotid endarterectomy: negative effects on cognitive performance. Clinical article. J Neurosurg 118:102310292013

4

Inoue TTsutsumi KAdachi STanaka SSaito KKunii N: Effectiveness of suturing training with 10-0 nylon under fixed and maximum magnification (x 20) using desk type microscope. Surg Neurol 66:1831872006

5

Inoue TTsutsumi KSaito KAdachi STanaka SKunii N: Training of A3-A3 side-to-side anastomosis in a deep corridor using a box with 6.5-cm depth: technical note. Surg Neurol 66:6386412006

6

International Study of Unruptured Intracranial Aneurysms Investigators: Unruptured intracranial aneurysms—risk of rupture and risks of surgical intervention. N Engl J Med 339:172517331998. (Erratum in N Engl J Med 340: 744 1999)

7

Ito Z: The microsurgical anterior interhemispheric approach suitably applied to ruptured aneurysms of the anterior communicating artery in the acute stage. Acta Neurochir (Wien) 63:85991982

8

Kobayashi MTakayama HSuga SOkazaki AMihara B: [Changes in proton magnetic resonance spectroscopy and Wechsler adult intelligence scale revised after clipping of unruptured aneurysms.]. No Shinkei Geka 28:6916982000. (Jpn)

9

Kubo YOgasawara KKashimura HOtawara YKakino SSugawara A: Cognitive function and anxiety before and after surgery for asymptomatic unruptured intracranial aneurysms in elderly patients. World Neurosurg 73:3503532010

10

Lal BKYounes MCruz GKapadia IJamil ZPappas PJ: Cognitive changes after surgery vs stenting for carotid artery stenosis. J Vasc Surg 54:6916982011

11

Little ASLiu SBeeman SSankar TPreul MCHu LS: Brain retraction and thickness of cerebral neocortex: an automated technique for detecting retraction-induced anatomic changes using magnetic resonance imaging. Neurosurgery 67:3 Suppl Operativeons277ons2822010

12

Morita AKirino THashi KAoki NFukuhara SHashimoto N: The natural course of unruptured cerebral aneurysms in a Japanese cohort. N Engl J Med 366:247424822012

13

Moroi JHadeishi HSuzuki AYasui N: Morbidity and mortality from surgical treatment of unruptured cerebral aneurysms at Research Institute for Brain and Blood Vessels-Akita. Neurosurgery 56:2242312005

14

Ohue SOka YKumon YOhta SSakaki SHatakeyama T: Importance of neuropsychological evaluation after surgery in patients with unruptured cerebral aneurysms. Surg Neurol 59:2692762003

15

Otawara YOgasawara KOgawa AYamadate K: Cognitive function before and after surgery in patients with unruptured intracranial aneurysm. Stroke 36:1421432005

16

Pereira-Filho AAPereira AGFaria MBLima LCSPortuguez MWKraemer JL: Microsurgical clipping in forty patients with unruptured anterior cerebral circulation aneurysms: an investigation into cognitive outcome. Arq Neuropsiquiatr 68:7707742010

17

Raaymakers TWMRinkel GJELimburg MAlgra A: Mortality and morbidity of surgery for unruptured intracranial aneurysms: a meta-analysis. Stroke 29:153115381998

18

Scott RBEccles FMolyneux AJKerr RSCRothwell PMCarpenter K: Improved cognitive outcomes with endovascular coiling of ruptured intracranial aneurysms: neuropsychological outcomes from the International Subarachnoid Aneurysm Trial (ISAT). Stroke 41:174317472010

19

Shimizu HInoue TFujimura MSaito ATominaga T: Cerebral blood flow after surgery for unruptured cerebral aneurysms: effects of surgical manipulation and irrigation fluid. Neurosurgery 69:6776882011

20

Sugishita M: [Japanese Wechsler Memory Scale-Revised.] TokyoNihon Bunka Kagakusha2001. (Jpn)

21

Tsutsumi KUeki KUsui MKwak SKirino T: Risk of subarachnoid hemorrhage after surgical treatment of unruptured cerebral aneurysms. Stroke 30:118111841999

22

Tuffiash ETamargo RJHillis AE: Craniotomy for treatment of unruptured aneurysms is not associated with long-term cognitive dysfunction. Stroke 34:219521992003

23

Wicks RTPradilla GRaza SMHadelsberg UCoon ALHuang J: Impact of changes in intraoperative somatosensory evoked potentials on stroke rates after clipping of intracranial aneurysms. Neurosurgery 70:111411242012

24

Wiebers DOWhisnant JPHuston J IIIMeissner IBrown RD JrPiepgras DG: Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 362:1031102003

25

Yamashiro SNishi TKoga KGoto TMuta DKuratsu J: Postoperative quality of life of patients treated for asymptomatic unruptured intracranial aneurysms. J Neurosurg 107:108610912007

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