Motor Evoked Potential Monitoring During Surgery of Middle Cerebral Artery Aneurysms: A Cohort Study

Motor Evoked Potential Monitoring During Surgery of Middle Cerebral Artery Aneurysms: A Cohort Study Qi Yue, Wei Zhu, Yuxiang Gu, Bin Xu, Liqin Lang, Jianping Song, Jiajun Cai, Geng Xu, Liang Chen, Ying Mao

Key words Aneurysm - Intraoperative monitoring - Middle cerebral artery - Motor evoked potential - Surgery

- BACKGROUND:

Abbreviations and Acronyms CT: Computed tomography MCA: Middle cerebral artery MEP: Motor evoked potential SSEP: Somatosensory evoked potential

- METHODS:

-

Motor evoked potential (MEP) monitoring has been widely used in brain or spine surgery to recognize potential damage of the pyramidal motor system. However, its ability to detect ischemic injury during middle cerebral artery (MCA) aneurysm surgery remains unclear. A prospective cohort study was designed to evaluate MEP changes during MCA aneurysm surgery.

To whom correspondence should be addressed: Ying Mao, M.D., Ph.D or Liang Chen, M.D., Ph.D. [E-mail: [email protected] or [email protected]]

From January 2009 to August 2011, 89 patients underwent MCA aneurysm surgery and were prospectively divided into 2 groups: MEP monitoring group and control group. Based on an amplitude decrement of >50% or loss, a 2-stage warning criterion of MEP changes was established. Concomitant somatosensory evoked potential changes were also recorded. MEP changes occurred in 15 patients, and various methods were used to avoid continued brain ischemia. Indocyanine green angiography and Doppler ultrasonography were performed if needed. A head computed tomography scan was performed immediately and the day after the operation.

Citation: World Neurosurg. (2014) 82, 6:1091-1099. http://dx.doi.org/10.1016/j.wneu.2014.09.004

- RESULTS:

Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China

Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2014 Elsevier Inc. All rights reserved.

INTRODUCTION With microsurgical technologies developing rapidly, great progress have been made in treatments for intracranial aneurysms over the past 2 decades (11, 12). However, postoperative ischemia rates can still be 10.3%, among which surgical factors play a principal role (7.6%) followed by vasospasm (2.3%) (21). Various surgical maneuvers, including temporary clipping, retraction, dissection, and vessel occlusion, may disturb focal circulation. If this situation is prolonged, irreversible damage of the affected brain tissue may occur (3). Although more patients are choosing less invasive endovascular therapy, patients with complicated aneurysms with a large volume, deep location, wide neck, or thick wall or recurrence after coiling must undergo open surgery. Instead of simple clipping, a complicated, time-consuming multiclip method or vessel reconstruction is needed to secure these aneurysms. These complicated procedures require prolonged parent artery occlusion and increase the risk of injuring perforating

At discharge, neither motor status nor Glasgow Coma Scale score was significantly different between the 2 groups. However, at the latest followup (mean, 31.9 months), motor status of the patients in the monitoring group was better (P [ 0.037). MEP monitoring was identified as an independent prognostic factor for motor outcome in long-term results by multivariate analysis (P [ 0.042). Both wave loss and >50% amplitude decrement of MEP monitoring showed good predictive value when used as part of a 2-stage warning criterion.

- CONCLUSIONS:

MEP monitoring is reliable for evaluation of the ischemic status of the pyramidal motor system during MCA aneurysm surgery and can improve surgical outcomes when used appropriately.

branches. A sensitive and specific method is needed to alert surgeons of possible ischemic injury in a timely fashion during operation. As a result of advances in bioelectrical engineering, intraoperative neurophysiologic monitoring has been applied more recently in operations involving eloquent cortex, spine, skull base, carotid stenosis, and aortic aneurysms to detect mechanical or ischemic damage caused by surgical procedures (15, 20, 23). With the help of intraoperative monitoring, surgeons are able to adjust procedures to avoid irreversible neurologic deficits. Somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) are the most widely used neurophysiologic monitoring methods. SSEPs can evaluate the sensory

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system, but when considering the motor system, false positive and negative predictive values are high (28). MEP monitoring, including transcranial and direct types, uses electrical stimulations targeted at primary motor cortex to produce depolarized action potentials that can be recorded along corticospinal tracts (13). With the refinement of total intravenous anesthesia as well as multiple-pulse stimulation, it has become feasible to monitor transcranial MEPs continuously during an operation (22). However, because of instability of MEPs and the unpredictable reaction of the brain to ischemia, the relationship between MEP changes and clinical outcome is unclear. Considering that the primary motor cortex is mainly supplied by the middle

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cerebral artery (MCA) and temporary occlusion of this vessel is often inevitable during MCA aneurysm clipping (19), we hypothesized that MEP monitoring may be effective in detecting motor impairment during surgery. A prospective cohort study on MEP monitoring and postoperative motor status in patients with MCA aneurysm was conducted. MATERIALS AND METHODS Patients Patients who presented with frequent seizures, infarction on computed tomography (CT) scan, obvious vasospasm on digital subtraction angiography preoperatively, or a history of metal implants such as cardiac pacemakers were excluded from this study. Patients with more than 1 intracranial aneurysm were also excluded. From January 2009 to August 2011, 89 patients who underwent MCA aneurysm surgery at Huashan Hospital performed by the same neurosurgical team were enrolled in the study. The patients were divided into 2 groups: MEP monitoring group (n ¼ 44) and control group (n ¼ 45). Because of ethical concerns, MEP monitoring was intentionally used in 3 cases: 2 saccular aneurysms >3 cm and 1 fusiform aneurysm >1.5 cm. Informed consent was obtained from all patients enrolled. Anesthesia Anesthesia was induced by a bolus intravenous injection of midazolam (0.03 mg/ kg), lidocaine (1 mg/kg), fentanyl (3e4 mg/ kg), and propofol (4e6 mg/mL), and tracheal intubation was performed with vecuronium (1 mg/kg). Before scalp incision, an additional 2 mg/kg of fentanyl was administered, and remifentanil (50e200 ng/kg/minute) was administered during the operation depending on the influence of various surgical procedures. Stable hemodynamics was maintained with propofol (3e5 mg/mL). In addition, blood pressure, temperature, heart rate, blood-oxygen concentration, and carbon dioxide concentration were monitored continuously. MEP and SSEP Monitoring Both kinds of monitoring were supervised by the operator. For MEP monitoring, corkscrew electrodes, placed subcutaneously at C3 and C4 positions, were used for

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stimulation (according to the International 10-20 System of Electrode Placement). Responses were received and recorded with use of 2-cm needle electrodes, inserted bilaterally in the upper abductor pollicis brevis and lower abductor hallucis muscle. Polarity settings could be reversed mechanically, and MEPs induced from the nonoperated hemisphere served as control responses. Stimulation intensity of 100e400 V was chosen when stable waves >100 mV were elicited in distal target muscles. Other parameters included interstimulus interval of 2 msec, stimulus duration of 0.1 msec, and short trains of 5 stimuli. Recordings after anesthesia, after dural incision, and before placement of temporary clips were collected for baseline analysis. MEPs were monitored approximately every 5 minutes throughout the operation. During critical procedures, such as aneurysm dissection, temporary clipping, and clip adjustment, MEP recording was repeated every 2 minutes or more frequently. To notify the surgeon promptly, a 2-stage warning criterion was established with >50% decrement of amplitudes as stage 1 and wave loss as stage 2. Wave loss was defined as >90% decrement of amplitudes. A bite-block was placed in the patient’s mouth to prevent bite injuries in case of masticatory muscle contraction caused by stimulations. For SSEP monitoring, metal bar electrodes were applied for transmitting stimuli. Median nerve at the wrist and posterior tibial nerve at the medial malleolus were chosen as stimulation sites. With 200 times average signals and 100-msec analysis time, stimulation-associated parameters such as intensity, frequency, and interval were adjusted to gain adequate SSEP waves. The time points for baseline determination were similar to MEP monitoring, and continuous recordings were then monitored during MEP intervals. A >50% decrement of amplitudes secondary to surgical procedures was regarded as a positive warning to alert the surgeon. Surgical Strategies Based on MEP Changes Direct clipping was our primary choice. For aneurysms with large size or difficult configuration, multiclip reconstructive clipping under temporary occlusion was adopted. Distal bypass construction was used if clipping is unachievable or there was

obvious MEP change that did not recover after adjustment. Surgical procedures were also adjusted according to MEP changes, including removing the temporary clips, adjusting the clip placement, or loosening the retractor to slacken the brain. Indocyanine green angiography and Doppler ultrasonography were performed if needed. Outcome Evaluation and Follow-Up Neurologic status and Glasgow Coma Scale score were evaluated preoperatively, immediately after extubation, at discharge, and whenever symptomatic motor deficits occurred. The first postoperative head CT scan was performed immediately after surgery, and a second CT scan was performed the day after surgery. CT angiography was performed before discharge to confirm complete security of the aneurysm. All patients were interviewed 3 months after discharge and 1 year later. At the latest follow-up, motor status and Karnofsky performance scale were assessed together to evaluate long-term outcome. Any motor deficit still persisting then was considered permanent. Motor status was defined as myodynamia according to neurologic examination. Abnormal motor status was diagnosed when myodynamia of any limb was below level V. Statistical Analysis For univariate comparisons of demographics and outcomes between the 2 groups, Fisher test and Mann-Whitney U test were used for categorical data and continuous data, respectively. Multivariate analysis of parameters’ prediction for motor status change was performed using a logistic regression method with 2 models. All potential parameters were first adopted in model A, and 3 parameters with the most significant P values were chosen as confounding factors for MEP monitoring (control vs. monitoring). Model B was conducted to show the influence of MEP monitoring on outcomes adjusted by confounding factors. Sensitivity, specificity, and positive and negative predictive values of MEP warning criteria for aggravation of motor status were calculated as described before (17). All statistical analyses were done by IBM SPSS Statistics version 20.0 (IBM Corp., Armonk, New York, USA). The ideal sample size was estimated by PASS software version 11.0.7 (NCSS, LLC, Utah, USA).

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RESULTS There were 89 patients enrolled in this cohort study, 53 men and 36 women, with a mean age of 49.6 years (range, 17e70 years). Of the aneurysms, 64 were ruptured, and 25 were asymptomatic. There was no significant difference in the baseline demographics between the 2 groups (Table 1). Permanent clipping was achieved in 81 cases, and bypass was performed in 8 cases. We were unable to elicit MEPs in 1 (2.3%) of the 44 monitored patients; SSEP waves were successfully recorded in all patients. No complications were found in relation to the neurophysiologic monitoring. Intraoperative MEP changes occurred in 15 patients, with wave loss in 10 patients and 50%e90% decrement in 5 (Table 2). MEP wave did not recover in 1 patient (case

number 9) at the end of surgery, and 2 patients had changes lasting for at least 1 hour (case numbers 7 and 8). Temporary occlusion of the MCA for aneurysm clipping was the most common cause for MEP changes (53%) followed by cerebral retraction (27%) and inappropriate placement of the permanent clips (20%). In addition, 5 transient and 2 permanent SSEP changes were recorded, 6 of which were associated with MEP changes. Motor status decline was detected in 3 patients immediately after surgery (case numbers 1, 9, and 12), and 5 patients had a new low-density area on postoperative CT scan (case numbers 1, 3, 9, 10, and 13). At discharge, 12 patients (27%) in the control group had aggravated motor deficit compared with 4 patients (9%) in monitoring group (Table 3). The

Table 1. Patient Demographics and Treatments Parameter

Monitoring

Control

Total

P Value

48.1  10.6

51.0  9.1

49.6  10.0

0.269

17e67

31e70

17e70

Male

25

28

53

Female

19

17

36

35

37

72

Age (years) Mean  SD Range Sex (n) 0.669

Size (n) Small (<1.5 cm)

0.925

DISCUSSION

Medium (1.5e2.4 cm)

4

3

7

Large (>2.4 cm)

5

5

10

Saccular

40

43

83

Spindle

4

2

6

SAH

28

36

64

Asymptomatic

16

9

25

14.8  0.8

13.8  2.5

14.3  2.0

0.098

39

38

77

0.758

5

7

12

39

42

81

5

3

8

Form (n) 0.434

Reason for admission (n) 0.103

Preoperative status GCS score (mean  SD) Motor status (n) Normal Abnormal Management (n) Clip Bypass

SAH, subarachnoid hemorrhage; GCS, Glasgow Coma Scale.

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monitoring group was followed for a mean of 30.3 months with 4 cases lost, whereas the control group was followed for a mean of 33.5 months with 6 cases lost. Patients from the monitoring group achieved better recovery for motor status (P ¼ 0.037). Multivariate analysis of MEP influence on patient outcome was performed in a 2-model method by adjusting possible confounding factors (Table 4). At the latest follow-up, age (P ¼ 0.010), reason for admission (asymptomatic vs. subarachnoid hemorrhage; P ¼ 0.109), and surgical management (bypass vs. clip; P ¼ 0.106) had the strongest correlation with motor status change in model A. Adjusted by the factors in model B, MEP monitoring (control vs. monitoring) showed an independent association with motor status change; patients without intraoperative MEP monitoring were nearly 4 times more likely to experience a decline in motor status than patients with intraoperative monitoring (odds ratio ¼ 4.77; P ¼ 0.042). Comparing sensitivity, specificity, and predictive values of the 2 stages of the warning criterion, stage 1 warning did much better in predicting ischemia on CT scan with higher sensitivity and predictive values, whereas stage 2 warning was more closely associated with aggravated motor status (Table 5). Nearly no risk of new motor deficit existed for patients without intraoperative warning.

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Impact of MEP Monitoring on Motor Outcomes In the present study, we prospectively investigated clinical outcomes of patients who underwent MCA aneurysm surgeries, demonstrating that MEP monitoring independently led to more favorable motor status. Over the past decade, many researchers have retrospectively analyzed the relationship between MEP changes and clinical outcomes, showing that MEP monitoring is good for risk warning and decision making during aneurysm surgery (8, 16, 27). However, this technique has not been routinely used in aneurysm surgery in many medical centers, and postoperative hemiplegia is still high after procedures for MCA aneurysms. A prospective randomized study enrolling both monitoring and nonmonitoring cases was needed to evaluate the MEP monitoring technique

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Duration of Preoperative Temporary Sex/Age Size Motor Clipping Case (years) (cm) Location Status (minutes) Causative Event

MEP Change

F/54

1.5 Right

Normal

2

M/19

3

Left hemiparesis: 2e3/5

21 Temporary clipping Loss to decrement >50%

3

F/55

0.8 Right

Normal

17 Temporary clipping Loss

4

F/49

1

Normal

5

F/48

0.7 Left

Right

Right

Normal

13, 21, 8, 8 Temporary clipping Loss

Loss

3, 9

Left hemiparesis: 2/5

Right frontal lobe and basal ganglia

Left KPS: 40; left hemiparesis: hemiparesis: 3e4/5 4/5

9

None

None

Left hemiparesis: 3/5

None

Left KPS: 80; epilepsy hemiparesis: 4e5/5

3

None

None

Normal

Right temporal lobe

Normal

KPS: 100; normal

9

None

None

Normal

None

Normal

KPS: 100; normal

13 Temporary clipping Loss

5

Decrement >50% 3

Normal

None

Normal

KPS: 100; normal

11, 12, 7 Temporary clipping Loss

4, 4

None

None

Normal

None

Normal

Lost

60

None

None

Normal

None

Normal

KPS: 90; headache

Decrement >50% Permanent Normal

None

Normal

KPS: 100; normal

Left basal ganglia

Right KPS: 60; right hemiparesis: hemiparesis: 1/5 3e4/5

12, 12 Temporary clipping Decrement >50% to loss

14, 20

SSEP Change

Clinical Outcome SSEP Change New LDA on Duration Postoperative Postoperative At At Last (minutes) Motor Status CT Discharge Follow-Up

M/36

0.9 Left

Normal

M/17

0.5 Left

Normal

8

F/25

3

Left

Normal

6, 21, 17 Temporary clipping Loss

9

F/59

1.2 Left

Normal

9 Permanent clipping Loss

10

M/48

0.4 Left

Normal

7 Permanent clipping Decrement >50%

4

None

None

Normal

Left frontal lobe

Normal

KPS: 80; left facial palsy

11

M/54

0.6 Right

Normal

20, 3 Permanent clipping Decrement >50%

7

None

None

Normal

None

Normal

KPS: 100; normal

12

F/44

1

Right

Normal

3,17,4 Retraction

Decrement >50%

2

None

None

Left hemiparesis: 4/5

None

Normal

KPS: 90; headache

13

F/57

1

Right

Normal

8 Retraction

Decrement >50%

9

None

None

Normal

Right basal ganglia

Normal

KPS: 90; headache

14

F/43

0.4 Right

Normal

8 Retraction

Decrement >50% to loss

6

Decrement >50% 1

Normal

None

Normal

KPS: 100; normal

15

M/43

3.5 Left

Normal

24 Retraction

Decrement >50% to loss

11

Decrement >50% 7

Normal

None

Normal

KPS: 100; normal

20, 34, 37 Temporary clipping Decrement >50%

15, 73

Permanent Decrement >50% Permanent Right hemiparesis: 0/5

MEP, motor evoked potential; SSEP, somatosensory evoked potential; LDA, low-density area; CT, computed tomography; M, male; F, female; KPS, Karnofsky performance score.

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1

MEP Change Duration (minutes)

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Table 2. Summary of Motor Evoked Potential Changes

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Table 3. Univariate Analysis of Outcomes According to Treatment Group Parameter

Monitoring

Control

Total

P Value

At discharge Time, day (mean  SD)

13.0  6.4

11.6  6.5

12.3  6.5

0.364

GCS (mean  SD)

15.0  0.3

13.6  3.1

14.3  2.3

0.067

Improved or same

40

33

73

0.051

Aggravated

4

12

16

Time (months) (mean  SD)

30.3  10.7

33.5  9.0

31.9  9.9

0.076

KPS (mean  SD)

91.5  16.1

80.0  29.2

85.8  24.1

0.094

Improved or same

37

29

66

0.037

Aggravated

3

10

13

Motor status change (n)

At last follow-up

Motor status change (n)

GCS, Glasgow Coma Scale; KPS, Karnofsky Performance Scale.

during MCA aneurysm surgery. Our study, although not completely randomized for ethical reasons, is the only prospective study to date. At about 12 days after operation, patients in the monitoring group did not show obvious motor improvement compared with controls, which may be explained by the fact that many patients who had experienced subarachnoid hemorrhage preoperatively had limb weakness not

relieved yet. At long-term follow-up, multivariate analysis revealed that MEP monitoring had a favorable effect on patients’ motor recovery and quality of life. Types of Electrical Stimulation Transcranial and direct electrical stimulations are alternative methods for MEP monitoring (14, 18). In 2007, Szelenyi et al. (25) used the 2 techniques in parallel and concluded that they do not differ in

Table 4. Multivariate Analysis of Motor Status Change at Last Follow-Up Model A Parameter

Model B

OR (95% CI)

P Value

OR (95% CI)

P Value

Age

1.13 (1.03e1.24)

0.010

1.08 (1.00e1.17)

0.042

Sex (female vs. male)

1.34 (0.28e6.37)

0.717

Size (large vs. medium, medium vs. small)

0.31 (0.04e2.45)

0.268

Form (spindle vs. saccular)

8.76 (0.41e188.11)

0.165

Reason for admission (asymptomatic vs. SAH)

0.27 (0.06e1.34)

0.109

0.39 (0.09e1.68)

0.207

Preoperative motor status (abnormal vs. normal)

0.85 (0.02e30.74)

0.927

Preoperative GCS score

0.75 (0.43e1.30)

0.300

21.19 (0.52e862.41)

0.106

3.58 (0.38e33.84)

0.267

4.93 (0.85e28.45)

0.075

4.77 (1.06e21.52)

0.042

Management (bypass vs. clip) MEP monitoring (control vs. monitoring)

OR, odds ratio; CI, confidence interval; SAH, subarachnoid hemorrhage; GCS, Glasgow Coma Scale; MEP, motor evoked potential.

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capacity of locating an impending lesion in the motor area or its efferent pathway. However, direct MEP has been reported to result in bridging vein rupture and electrochemical neuronal injury (7, 13). In our study, transcranial MEP was adopted because a small craniotomy can be done safely and quickly and is optimal for aneurysm clipping in most cases. Only in 1 patient, for an unknown reason, we failed to elicit MEP waves. No complications, such as seizures, bite injury, scalp burn, or arrhythmia, were observed during the surgical procedure. However, there was slight head movement because of muscular contraction at stimulus, and the operator was reluctant to stop manipulation to wait for head movement to stop. Warning Criterion of MEP Monitoring Because of instability and complexity of MEP waves, there has been no widely accepted warning criterion for MEP monitoring up to now. Prolonged latency is used by a few centers (16). Based on our experiences, prolonged latency occurs too early and the length of latency is sometimes too obscure to be measured. Amplitude changes are more intuitionistic and almost always accompanied by prolonged latency, and similar to many other surgeons, we prefer to use amplitude change as the warning sign. However, there is no consensus regarding this criterion. Some authors regarded >50% decrease of MEP amplitude as a striking sign (7, 25, 29), whereas others tended to use loss of MEP wave to indicate likely damage (9). In the present study, we established for the first time a 2-stage warning criterion and tested its correlation with patient outcome. Stage 1 warning was more sensitive to radiologic abnormality, whereas stage 2 warning predicted motor status decline better. This result, together with our finding in 3 patients (case numbers 4, 14, and 15) who experienced a changeover from 50% decrement to loss of waves, indicates the importance of active interventions when MEP amplitude decreases by >50%. To avoid irreversible ischemic damage, it is essential to make every effort to shorten the time window between the 2 stages. Comparison Between MEP and SSEP Monitoring SSEP monitoring has been applied in brain surgery for many years, but former

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Table 5. Sensitivity, Specificity and Predictive Values of 2-Stage Warning Criterion Stage 1 (MEP decrement > 50%)

Stage 2 (MEP loss)

Parameter

Se

Sp

PPV

NPV

Se

Sp

PPV

NPV

New LDA on postoperative CT

0.71

0.72

0.33

0.93

0.43

0.81

0.30

0.88

At discharge

0.50

0.67

0.13

0.93

0.50

0.84

0.20

0.95

At latest follow-up

0.67

0.68

0.14

0.96

0.67

0.81

0.22

0.97

New motor deficit

MEP, motor evoked potential; Se, sensitivity; Sp, specificity; PPV, positive predictive value; NPV, negative predictive value; LDA, low density area; CT, computed tomography.

studies in aneurysm surgery demonstrated it to be inferior to MEP. There were 33 cases of motor deterioration in the series by Neuloh and Schramm (16); 19 were detected by MEP, but only 5 were detected by SSEP. Yeon et al. (29) detected 12 MEP changes in 99 cases, whereas only 4 patients showed SSEP decrement. Changes of MEP were not always in accordance with SSEP in our research.

Among the 15 cases with MEP changes, only 6 were associated with SSEP decreases, and 2 of the 6 developed new motor deficits after surgery. There was only 1 patient in our cohort who demonstrated positive SSEP decrement but negative MEP change. SSEPs severely descended 13 minutes after temporary occlusion and recovered immediately after clip removal. No radiologic ischemia or motor deficit

Figure 1. Case 3. Computed tomography scan showed a subarachnoid hemorrhage in the right lateral fissure (A), and a right M1 bifurcation aneurysm was shown on digital subtraction angiography with posteroanterior (B) and oblique (C) views. The motor evoked potential wave disappeared 15 minutes after temporary occlusion of M1 and recovered immediately (36 seconds) after removal of the clip (D, yellow

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occurred. Similarly, Yeon et al. (29) observed isolated SSEP changes in 1 patient with an M2 aneurysm who experienced no clinical deterioration later. Supporting this result, primary sensory cortex lies at the posterior margin of MCA territories and can get better cortical collateral flow from branches of the posterior cerebral artery (4, 30). Deep structures with a sensory pathway, such as the thalamus, are mainly supplied by perforators from the posterior circulation (30). SSEP monitoring is theoretically less specific or sensitive in finding ischemia in the motor cortex or motor pathway, which made it less valuable for MCA aneurysm surgery. However, SSEP monitoring plays an important role in predicting large area ischemia (10). In the event transcranial electrical MEP monitoring bypasses the hypoperfused cortex and excites the subcortical tract, SSEP monitoring would detect this and reduce false-negative potentials reflecting blood supply of the motor cortex. In addition, based on our experience, SSEP changes on the left side

box, with details presented in the right panel). Arrowheads (D) represent temporary clipping (top), permanent clipping (middle), and removal of temporary clip (bottom). No change in somatosensory evoked potentials occurred throughout the operation (E). Postoperative computed tomography (F) showed a small low-density area at the right temporal lobe.

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Figure 2. Case 5. A left M1 bifurcation aneurysm was shown on computed tomography angiography (A) and digital subtraction angiography with posteroanterior view (B). The motor evoked potential wave disappeared 10 minutes after temporary occlusion of M1 and recovered 2 minutes after removal of the clip. No abnormality was present after this (C). The somatosensory evoked potential wave decreased by 50% amplitude 10 minutes after temporary occlusion of M1 and recovered 3 minutes later. No change was present around removal of the temporary clip and placement of the permanent clip (D). Arrowheads (D) represent temporary clipping (top), removal of temporary clip (middle), and permanent clipping (bottom). No low-density area was found on postoperative CT (E).

might predict dysphasia for right-handed people, suggesting SSEP monitoring as a better tool than MEP monitoring to recognize ischemia of language area. Besides evoked potentials, electroencephalography was another neurophysiologic method suggested to detect ischemia during aneurysm surgery and assess cortical perfusion in various intraoperative procedures (1). Electroencephalography was also performed during our operations but was used by the anesthiologists to determine the depth of anesthesia. In their opinion, burst suppression on electroencephalography indicated decreased cerebral metabolic rate and increased tolerance to ischemia, so it was stably maintained throughout temporary occlusion. These

relatively low waves provided little value for predicting infarction and were not analyzed further in our study. MEP Monitoring and Time Window of Safe MCA Occlusion The time window of safe occlusion of M1 or M2 had been supposed to be 15e20 minutes (5); however, this is inaccurate, and there are often cases with symptomatic infarction after a very short time of parent artery occlusion. There might be other iatrogenic reasons resulting in unfavorable outcomes, but nevertheless a more reliable alarm method is needed to make temporal MCA occlusion safer. Intraoperative MEP monitoring acts as a real-time and casesensitive method in detecting ischemic

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damage that has affected spiking activity of the primary motor cortex or its conduction in pyramidal motor tract, and it can suggest the time window of safe occlusion (6). This time window is very important for operators to adjust surgical procedures or change surgical strategy in time during the operation. For example, with infarction of basal ganglia, an instant decrement in MEPs following temporary occlusion always indicates compromise of perforators, so the surgeon should quickly examine whether perforators, especially the lateral ones, are misclipped and adjust the placement of clips accordingly. Otherwise, contralateral paralysis may be inevitable (2). With an average duration of 9 minutes, we performed persistent MEP monitoring

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during temporary clipping. MEP waves disappeared 15 minutes after temporary clipping of M1 in case number 3 and recovered immediately (36 seconds) after removal of the clip (Figure 1). Although postoperative CT scan showed a lowdensity area at the right temporal lobe, the patient did not demonstrate any motor deficit during our follow-up. Temporary occlusion of the MCA was the most common cause for MEP changes (53%) in our series, followed by cerebral retraction (27%) and inappropriate permanent clipping (20%). The mean time from temporal clip placement to MEP change (>50% amplitude decrement or wave loss) was 9 minutes (range, 4e15 minutes). False-Positive or False-Negative Analysis Sensitivity and positive predictive value for MEPs are not high according to the literature (6). Szelenyi et al. (26) reported a 0.5 sensitivity and a 0.63 positive predictive value, and these data were updated to 0.6 and 0.3 in a follow-up article (25). Consistent with these studies, MEP monitoring showed similar sensitivity and positive predictive value in our study. High falsepositive findings probably resulted from our prompt surgical reactions to invert temporary injuries in case of MEP changes, such as suspending temporary occlusion, repositioning clips, alleviating pressure on retractors, or just paying more attention to maneuvering. For example, in case number 5, both MEP and SSEP waves decreased about 10 minutes after temporary clipping of M1 and returned to baseline early after removal of the clip. We then directly clipped the aneurysm without temporary occlusion. The patient showed no abnormality later (Figure 2). As we expected and in accordance with other studies, negative predictive value in this study was high under the combination of MEP and SSEP monitoring. Only 1 patient with negative waves on both MEP monitoring and SSEP monitoring had permanent motor function decline. On one hand, as a result of administration of vecuronium, a muscle relaxant, during intubation, all baselines of MEPs were very low except in the left upper extremity. As the potency of vecuronium faded and subsequent waves returned to a higher form, actual decrease of MEP amplitude might not reach warning criteria compared with baselines. On the other hand, the

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MEP-stimulating voltage used for this patient was 400 V, which is relatively high enough to bypass the ischemic motor cortex or internal capsule and directly stimulate subcortical structures such as medulla oblongata (24). LIMITATIONS The present study has some limitations. First, although we performed this cohort study to confirm the effect of MEP monitoring on postoperative morbidity in MCA aneurysm surgery, ethical concerns prevented ideal randomization. With regard to huge or spindle aneurysms, we were inclined to proceed with MEP monitoring for the assumed benefits in the late stage. Second, the sample size is not big enough to ensure the difference of long-term recovery between 2 cohorts is really significant. Under a power of 0.8 and a significant level of 0.05, 63 patients per group are required to obtain an 18% reduction in morbidity. Third, our response to MEP changes and associated methodology improved over the course of research, probably influencing outcome. CONCLUSIONS In this study, we prospectively investigated clinical outcomes of patients who underwent MCA aneurysm surgeries, demonstrating that MEP monitoring, with a 2-stage warning criterion, independently led to more favorable motor status. Intraoperative MEP monitoring acts as a real-time and case-sensitive method for detecting ischemic damage and is effective for risk warning and decision making in MCA aneurysm surgery. ACKNOWLEDGMENTS The authors thank Antoun Koht, M.D. (Feinberg School of Medicine, Northwestern University), for instructions in designing the study, and Jesse Winer, M.D. (Department of Neurological Surgery, University of South California), for help in revising the manuscript. REFERENCES 1. Bacigaluppi S, Fontanella M, Manninen P, Ducati A, Tredici G, Gentili F: Monitoring techniques for prevention of procedure-related ischemic damage in aneurysm surgery. World Neurosurg 78:276-288, 2012.

2. Chen L, Lang L, Zhou LF, Song DL, Mao Y: Bypass or not? Adjustment of surgical strategies according to motor evoked potential changes in large middle cerebral artery aneurysm surgery. World Neurosurg 77:391-398, 2012. 3. Fraser JF, Riina H, Mitra N, Gobin YP, Simon AS, Stieg PE: Treatment of ruptured intracranial aneurysms: looking to the past to register the future. Neurosurgery 59:1157-1166; discussion 1166-1167, 2006. 4. Gibo H, Carver CC, Rhoton AJ, Lenkey C, Mitchell RJ: Microsurgical anatomy of the middle cerebral artery. J Neurosurg 54:151-169, 1981. 5. Griessenauer CJ, Poston TL, Shoja MM, Mortazavi MM, Falola M, Tubbs RS, Fisher WS: The impact of temporary artery occlusion during intracranial aneurysm surgery on long-term clinical outcome: part I. Patients with subarachnoid hemorrhage. World Neurosurg 82:140-148, 2014. 6. Guo L, Gelb AW: The use of motor evoked potential monitoring during cerebral aneurysm surgery to predict pure motor deficits due to subcortical ischemia. Clin Neurophysiol 122: 648-655, 2011. 7. Horiuchi K, Suzuki K, Sasaki T, Matsumoto M, Sakuma J, Konno Y, Oinuma M, Itakura T, Kodama N: Intraoperative monitoring of blood flow insufficiency during surgery of middle cerebral artery aneurysms. J Neurosurg 103:275-283, 2005. 8. Irie T, Yoshitani K, Ohnishi Y, Shinzawa M, Miura N, Kusaka Y, Miyazaki S, Miyamoto S: The efficacy of motor-evoked potentials on cerebral aneurysm surgery and new-onset postoperative motor deficits. J Neurosurg Anesthesiol 22: 247-251, 2010. 9. Kang DZ, Wu ZY, Lan Q, Yu LH, Lin ZY, Wang CY, Lin YX: Combined monitoring of evoked potentials during microsurgery for lesions adjacent to the brainstem and intracranial aneurysms. Chin Med J (Engl) 120:1567-1573, 2007. 10. Krayenbuhl N, Sarnthein J, Oinas M, Erdem E, Krisht AF: MRI-validation of SEP monitoring for ischemic events during microsurgical clipping of intracranial aneurysms. Clin Neurophysiol 122: 1878-1882, 2011. 11. Lanzino G, Burrows AM, Tymianski M: Advances in stroke: vascular neurosurgery. Stroke 44: 316-317, 2013. 12. Li H, Pan R, Wang HX, Rong XM, Yin Z, Milgrom DP, Shi XL, Tang YM, Peng Y: Clipping versus coiling for ruptured intracranial aneurysms: a systematic review and meta-analysis. Stroke 44: 29-37, 2013. 13. Macdonald DB: Intraoperative motor evoked potential monitoring: overview and update. J Clin Monit Comput 20:347-377, 2006. 14. Maruta Y, Fujii M, Imoto H, Nomura S, Oka F, Goto H, Shirao S, Yoshikawa K, Yoneda H, Ideguchi M, Suehiro E, Koizumi H, Ishihara H, Kato S, Kajiwara K, Suzuki M: Intra-operative monitoring of lower extremity motor-evoked potentials by direct cortical stimulation. Clin Neurophysiol 123:1248-1254, 2012.

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Conflict of interest statement: This study was sponsored by National Key Technology R&D Program of the Ministry of Science and Technology of China (Grant No. 2011BAI08B06 to Y. Mao), Shanghai Hospital Developing Center (Grant No. SHDC12010118 to Y. Mao), National Natural Science Foundation of China (Grant No. 81100860 to L. Chen), and Science Foundation for Youth Scholars of Public Health Bureau of Shanghai (Grant No. 2009Y-004 to L. Chen). Received 5 November 2013; accepted 3 September 2014; published online 8 September 2014 Citation: World Neurosurg. (2014) 82, 6:1091-1099. http://dx.doi.org/10.1016/j.wneu.2014.09.004 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2014 Elsevier Inc. All rights reserved.

WORLD NEUROSURGERY’S PEER REVIEW PROCESS All articles appearing with peer review designation have undergone a strict independent peer review process comprised of a minimum of six reviewers and the Editor-in-Chief. Reviewing panels are comprised of individuals who have earned positions of authority in the area related to the manuscript. In their composition, consideration is given to geographic location and widespread diversity of opinion. Every possible effort is made to exclude personal bias in decision making. Michael L.J. Apuzzo, M.D., Ph.D. (hon)

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