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　Original Contribution Kitasato Med J 2017; 47: 148-159　

Received 23 May 2017, accepted 1 August 2017Correspondence to: Sumito Sato, Department of Neurosurgery, Kitasato University School of Medicine1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, JapanE-mail: sumito@med.kitasato-u.ac.jp

Significance of cathodal stimulation formotor evoked potential monitoring

Sumito Sato,1 Yuya Onozawa,2 Mari Kusumi,1 Hiroyuki Koizumi,1

Keika Hoshi,3 Hirotsugu Okamoto,4 Toshihiro Kumabe1

1 Department of Neurosurgery, Kitasato University School of Medicine2 Clinical Laboratory, Kitasato University Hospital3 Department of Hygiene, Kitasato University School of Medicine4 Department of Anesthesiology, Kitasato University School of Medicine

Objective: Intraoperative motor evoked potential (MEP) monitoring is essential to reduce the risk ofneurosurgical procedures damaging the motor system. The standard technique of recording MEP useshigh-frequency anodal monopolar stimulation of the primary motor cortex. The present studyinvestigated the possibility that cathodal stimulation allows MEP recording at lower intensities thandoes anodal stimulation in certain patients.Methods: Motor threshold (MT) was measured and compared for anodal and cathodal stimulation in65 patients in Kitasato University Hospital. The patients were divided into 3 groups based on thepolarity of the lower MT: anodal less than cathodal stimulation (Group A), cathodal less than anodalstimulation (Group B), and anodal similar to cathodal stimulation (Group C). Magnetic resonance(MR) imaging findings of hyperintensity extending to the precentral knob accompanied by braintumor were evaluated to correlate with the polarity of lower MT.Results: There were 32 patients classified as Group A, 23 patients as Group B, and 10 patients asGroup C. MR imaging showed positive findings in 3 of 32 patients in Group A, 15 of 23 patients inGroup B, and 1 of 10 patients in Group C.Conclusions: Cathodal stimulation allows MEP recording at lower intensities than does anodalstimulation in a significant number of patients. MR imaging findings of hyperintensity extending tothe precentral knob may be indicative of appropriate cases for cathodal stimulation.

Key words: motor evoked potential, cathodal stimulation, brain tumor, precentral knob, edema

Introduction

ntraoperative motor evoked potential (MEP)monitoring is essential to reduce the risk of

neurosurgical procedures damaging the motor system.High-frequency anodal monopolar stimulation of theprimary motor cortex elicits compound muscle actionpotentials (CMAPs), which are detected as myogenicMEPs, even under general anesthesia,1-3 and it is thestandard MEP monitoring technique. However, if high-current intensity stimulation is needed to elicit targetmuscle contraction, unnecessary body motion ofteninterferes with microsurgical procedures.2 In addition,excessive charge density causes neural tissue damage,4,5

so that the stimulus intensity should be as low as possible

for safe MEP monitoring, which requires repetitivestimulation of the motor cortex for long operativedurations.

We unexpectedly discovered that MEPs were elicitedwith cathodal stimulation at substantially lower currentintensities than those required for anodal stimulation inpatients with a metastatic brain tumor. We have sincestudied the significance of cathodal stimulation for saferMEP monitoring using the lowest stimulus intensitypossible. Furthermore, T2-weighted magnetic resonance(MR) imaging of the original patient showedhyperintensity extending to the precentral gyrus indicatingperitumoral edema. Therefore, we also examined thepossible relationship between this MR imaging findingand the observed lower intensity of cathodal stimulation

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than that required for anodal stimulation to elicit MEPs.

Methods

PatientsThis study included 65 patients, 27 men and 38 womenaged 7 to 79 years old (mean 55.7 years), who underwentintraoperative MEP monitoring during surgery for theresection of newly diagnosed tumorous lesions in 49patients and for neck clipping of unruptured cerebralaneurysms in 16 patients in Kitasato University Hospitalfrom August 2011 to May 2016. Our criteria forutilization of intraoperative MEP monitoring were asfollows. The lesions were located around the motor cortexand/or the pyramidal tract and involved the arteriessupplying the motor cortex and/or the descending motorpathway. Patients with previous craniotomy wereexcluded because their brain tissue with induced organicchanges, such as cortical adhesion to the dura mater orscar formation, could affect the morphological and/orfunctional characteristics of pyramidal neurons. Writteninformed consent was obtained from all the patients. TheEthics Committee of Kitasato University Hospitalapproved this retrospective study on June 6, 2017 (B16-223).

Anesthesia and neurophysiological monitoringSurgery was performed under general anesthesiaadministered by anesthesiologists with propofol (targetcontrolled infusion: 2−4μg/ml at the affected site) andremifentanil (0.15−0.25μg/kg/min) without the use ofa muscle relaxant except during the short time requiredfor tracheal intubation. No other agents that could affectmotor function during MEP monitoring were used.Neurophysiological monitoring was performed using anevoked potential measuring system (Neuropack; NihonKohden, Tokyo).

Cortical recording of somatosensory evoked potentials(SEPs)Somatosensory evoked potentials (SEPs) were evokedby stimulation of the contralateral median nerve at thewrist and recorded using subdural electrodes (UniqueMedical, Tokyo) immediately prior to recording MEPsto identify the central sulcus by detecting the N20-P20phase reversal. The N20, a negative peak with a latencyof approximately 20 ms, is recorded from the postcentralregions, whereas the P20, a positive peak with the samelatency, is recorded from the precentral regions. Thus, aphase reversal should be observed at the level of thecentral sulcus. Both the amplitude between the peak and

the baseline and the peak latencies of N20 or P20 werealso measured. The appropriate type of subduralelectrodes was selected from 3 types: arrays of 4 × 1, 4× 2 (circular contact surfaces of 3-mm diameter, center-to-center spacing 10 mm), and 4 × 4 (2-mm diameter,spacing 6 mm) for each operative field.

Measurement of motor threshold (MT)Electrical stimulation for the recording of MEPs wasapplied through the same subdural electrodes used torecord SEPs located around the central sulcus usingmonopolar currents with 5 trains of monophasic squarewave pulses for 0.5 ms with an interstimulus interval of2 ms. A reference electrode was placed on thecontralateral mastoid process (early series) or on thesubdermal surface inside the skin flap (late series). Pairedneedle electrodes made of stainless steel (Nihon Kohden)were inserted into the contralateral thenar muscle to recordCMAPs as myogenic MEPs.

The stimulus current intensity eliciting thenar musclecontractions with a CMAP amplitude of approximately50μV was defined as the motor threshold (MT), inaccordance with the definition of transcranial magneticstimulation of the International Federation of ClinicalNeurophysiology.6 The MTs were measured in eachelectrode on the cortical surface using both anodal andcathodal stimulation to measure the minimum MT andstimulus polarity.

Classification based on the polarity of lower MTsThe patients were divided into three groups by comparingthe minimum MT of each stimulus polarity: Group Awith an anodal MT lower than the cathodal MT (differenceof 1 mA or more), Group B with a cathodal MT lowerthan the anodal MT (difference of 1 mA or more), andGroup C with very similar anodal and cathodal MTs(difference less than 1 mA).

Clinical manifestations and MEP monitoringPre- and postoperative motor functions were evaluatedby the manual muscle testing (MMT) score: 0, nocontraction; 1, flicker or trace contraction; 2, activemovement with gravity eliminated; 3, active movementagainst gravity; 4, active movement against resistance;and 5, normal strength. Postoperative score was finallyassessed after transient motor hypofunction within 3months in some patients. The stimulus polarity forintraoperative MEP monitoring was anodal in Group A,cathodal in Group B, and the better of either anodal orcathodal in Group C. The stimulus intensity wasdetermined based on the minimum current required to

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Table 1-1. Clinical characteristics

Age SEPCase

(years) DiagnosisNo.

Sex Phase Stimulus Latency Amplitudereversal site (ms) (μV)

Group A 1 52, F lt parietal, metastasis + P20 22.5 36.4 2 25, M rt parietal, tumefactive multiple sclerosis + N20 18.9 14.4 3 28, F rt parietal, cavernous hemangioma + P20 20.7 18.1 4 50, F lt parietal, glioblastoma + P20 21.5 121.4 5 19, F rt insulo-opercular, diffuse astrocytoma + P20 21.1 52.6 6 37, M lt insular, anaplastic astrocytoma − P20 20.5 21.8 7 72, M lt temporal, glioblastoma + N20 21.6 32.6 8 40, M rt thalamic, glioblastoma − P20 24.7 8.9 9 44, F rt insulo-opercular, anaplastic astrocytoma − P20 19.4 19.310 57, F rt parietal-temporal, glioblastoma − − − −

11 35, F rt sphenoid ridge, meningioma − P20 18.1 8.812 37, M rt thalamic, glioblastoma + P20 20.1 105.313 67, M rt frontal, anaplastic oligodendroglioma + P20 19.8 39.414 43, M rt thalamic, glioblastoma + P20 21.7 43.615 51, F lt thalamic, glioblastoma + P20 22.9 4.216 65, F lt frontal, glioblastoma − − − −

17 29, F lt insular, glioblastoma + P20 21.5 122.618 64, F rt MCB An, unruptured + N20 20.1 35.519 63, F rt MCB An, unruptured + P20 21.2 36.920 68, F rt IC-Pcom An, unruptured + P20 19.9 27.621 71, F rt MCB An, unruptured + P20 19.7 28.222 71, F rt MCB An, unruptured + P20 20.1 8.323 69, F lt IC-Pcom An, unruptured + P20 21.1 34.224 75, M rt MCB An, unruptured − N20 22.4 8.325 59, F rt MCB An, unruptured − P20 20.7 18.426 39, F rt MCB An, unruptured − P20 21.1 5.227 63, F lt MCB An, unruptured + P20 21.4 28.228 68, F lt IC-Pcom An, unruptured − P20 20.0 18.329 33, F rt MCB An, unruptured − P20 22.4 8.130 71, F rt MCB An, unruptured + P20 22.9 29.531 50, F rt MCB An, unruptured − P20 22.1 12.332 69, F rt MCB An, unruptured + P20 21.8 24.0

elicit reproducible MEPs during surgery. MEPs werecontinuously recorded at an interval of 1 minute (or 30seconds, as necessary) until displacement of subduralelectrodes.

MR imaging findingsT2-weighted MR imaging findings were examined toidentify hyperintensity, indicating peritumoral edema and/or tumor infiltration, extending to the precentral knobthat contains the motor hand area as the stimulus site ofMEP recording from the thenar muscle.7

Relationship between the amplitude of P20 and that ofthe MTTo verify that the electrodes were appropriately locatedjust on the motor hand area, the amplitude of P20generated at the sensory hand area by stimulation of themedian nerve was measured. The relationship betweenthe amplitude of P20 and that of the MT was evaluated.

Statistical analysisAll statistical analyses were conducted using JMPsoftware (JMP 10; SAS Institute, Cary, NC, USA).

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Cathodal stimulation for MEP monitoring

MEP (mA)T2

Anodal Cathodal Difference high

13.2 21.8 8.6 + 8.8 >10.0 >1.2 −

10.0 12.0 2.0 −

4.8 8.6 3.8 −

7.9 9.6 1.7 −

11.5 13.2 1.7 −

11.4 >15.0 >3.6 + 8.9 10.9 2.0 −

13.0 17.4 4.4 −

4.8 7.3 2.5 −

13.8 18.0 4.2 −

7.8 9.8 2.0 −

7.2 12.9 5.7 −

14.7 >16.0 >1.3 −

9.2 13.3 3.1 −

7.9 >20 >12.1 −

7.5 9.5 2.0 + 8.2 16.8 8.6 −

7.7 10.5 2.8 −

11.7 >15.0 >3.3 −

8.3 13.4 5.1 −

6.1 12.6 6.5 −

5.0 7.0 2.0 −

16.7 >20.0 >3.3 −

8.2 14.8 6.6 −

12.3 >20.0 >7.7 −

9.8 >20.0 >10.2 −

14.7 >20.0 >5.3 −

9.8 >20.0 >10.2 −

12.6 >20.0 >7.4 −

23.8 >30.0 >6.2 −

9.0 13.5 4.5 −

Results

Cortical SEPsCortical SEPs were successfully recorded in 63 of the 65patients, due to technical errors in 2 patients. The N20-P20 phase reversal was found in 44 of 63 patients. Theprimary hand-motor cortex was not exposed in theoperative field in most cases, so the subdural electrodeswere slid into the subdural space toward the central region.Most cases without N20-P20 phase reversal only showedP20 in all electrodes. Both the latency and the amplitudeof P20 recorded at the electrode where the minimum MTwas obtained were not significantly different betweenGroups A and B (Kruskal-Wallis test) (Table 1).

MT in each groupGroup A was composed of 32 patients with MT from 4.8to 23.8 (10.1 ± 3.8) mA, Group B was composed of 23patients with MT from 2.7 to 27.0 (8.4 ± 5.7) mA, andGroup C was composed of 10 patients with MT from 2.8to 9.6 (6.4 ± 1.9) mA. Differences in MT from theopposite polarity threshold were 1.7 to more than 12.1mA in Group A, and from 1.0 to more than 11.6 mA inGroup B. Patients with an aneurysm were mainlyclassified into Group A, with none in Group B, and onlyone in Group C. The locations of the electrodes withminimum MTs at each polarity coincided in most cases(Table 1).

MEP monitoring and clinical outcomeStimulus intensities for intraoperative MEP monitoringranged from 7.0 to 25.0 (13.6 ± 4.3) mA in Group A, 5.0to 28.0 (12.1 ± 5.7) mA in Group B, and 4.0 to 14.0 (9.1± 2.6) mA in Group C. Motor function deteriorated in5 patients: 2 patients with MMT scores changing from 5to 2 and 4 to 3 in Group A, and 3 patients with MMTscores changing from 4 to 2, 5 to 4, and 5 to 3 in GroupB. MEP amplitudes reduced to 0%, 6%, 67%, 60%, and67%, respectively, compared with the control values.Final MEP amplitude was reduced to less than 50% ofcontrol without clinical manifestations (false positive) in3 patients in Group A and in 5 patients in Group B (Table2).

MR imaging findingsHyperintensity extending to the precentral knob on T2-weighted imaging was present in 3 of 32 patients in GroupA, in 15 of 23 patients in Group B, and in 1 of 10 patientsin Group C. Presence of hyperintensity on MR imagingwas significantly higher in Group B (P < 0.001, Fisher'sexact test) (Table 3).

Validation of electrode locationsSignificant negative correlation was demonstratedbetween the amplitudes of P20 and the MT (Pearson'scorrelation coefficient, -0.616) (Figure 1). The amplitudesof P20 showed no significant differences between GroupsA and B. Therefore, the location of the electrodes causedno differences between Groups A and B.

Illustrative case (Case 38, Group B)A 71-year-old man with a pulmonary lesion on chestcomputed tomography gradually developed righthemiparesis over 2 months. Preoperative MMT scorewas 4 in the left upper extremity. MR imaging showed aring-enhanced mass suspected to be a metastatic tumor

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Table 1-2. Clinical characteristics

Age SEPCase

(years) DiagnosisNo.

Sex Phase Stimulus Latency Amplitudereversal site (ms) (μV)

Group B33 71, F rt frontal, glioblastoma + P20 22.7 148.534 46, M rt parieto-temporal, oligoastrocytoma + P20 21.6 76.835 77, M lt frontal, glioblastoma + P20 21.9 16.336 55, F lt parietal, glioblastoma + P20 20.2 55.137 71, M lt frontal, glioblastoma + P20 24.5 50.738 71, M lt parietal, metastasis + P20 22.2 18.139 43, M lt middle fossa, schwannoma + P20 21.3 175.240 71, M lt parietal, glioblastoma + P20 23.2 27.541 19, F rt intraventricular, meningioma + P20 21.3 52.642 56, M rt intraventricular, ependymoma + P20 21.1 31.343 63, F rt parietal, glioblastoma + P20 21.2 13.144 42, M lt insulo-opercular, anaplastic astrocytoma − P20 19.1 56.945 70, F lt parietal, glioblastoma + P20 21.5 50.146 7, F lt optic tract, pilocytic astrocytoma − P20 17.5 9.047 72, M lt insular-basal ganglia, glioblastoma − P20 19.9 59.448 50, F lt frontal, metastasis − P20 20.2 12.049 41, M rt insulo-opercular, anaplastic oligodendroglioma − P20 18.4 18.850 12, F lt intraventricular, atypical choroid plexus papilloma + P20 19.1 53.851 64, F lt posterior cingulate, glioblastoma − P20 19.8 82.652 42, F lt convexity, meningioma − N20 18.6 9.253 67, M lt parietal, glioblastoma + P20 20.4 33.854 73, F lt parietal, glioblastoma + P20 20.6 50.055 76, F rt parietal-cingulate, glioblastoma + P20 22.0 51.3

Group C56 71, M lt frontal, glioblastoma + P20 22.7 146.457 61, F lt frontal, anaplastic oligodendroglioma + P20 17.6 33.258 59, M rt frontal, anaplastic oligodendroglioma + P20 22.4 40.059 74, M rt parietal, glioblastoma + P20 24.2 81.360 64, M rt temporal, glioblastoma + P20 23.4 156.461 73, M lt frontal, anaplastic oligodendroglioma + P20 22.9 41.362 79, M lt temporal, glioblastoma − P20 23.6 125.163 66, M lt hypothalamic, pilocytic astrocytoma + P20 21.5 60.764 59, M lt thalamic, glioblastoma − P20 21.7 40.065 71, F rt MCB An, unruptured + P20 24.9 117.9

Sato S. et al.

M, male; F, female; rt, right; lt, left; SEP, somatosensory evoked potential; MEP, motor evoked potential; MCB, middle cerebralartery bifurcation; An, aneurysm; IC-Pcom, internal carotid-posterior communicating; T2 high, hyperintensity extending to theprecentral knob on T2-weighted imaging

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MEP (mA)T2

Anodal Cathodal Difference high

8.4 5.6 2.8 −

11.0 9.0 2.0 +>35.0 27.0 >8.0 +

7.4 6.0 1.4 +12.0 8.0 4.0 +

>15.0 9.0 >6.0 +5.4 4.4 1.0 −

10.5 6.0 4.5 +10.5 9.0 1.5 +

7.6 6.3 1.3 −

13.0 7.2 5.8 +7.6 4.8 2.8 −

7.0 4.8 2.2 +>15.0 13.0 >2.0 −

5.6 4.5 1.1 −

>20.0 8.4 >11.6 +12.0 9.0 3.0 −

7.2 6.0 1.2 −

9.3 6.1 3.2 +>25.0 23.6 >1.4 +

5.7 4.7 1.0 +10.4 7.7 2.7 +

4.0 2.7 1.3 +

4.7 4.5 0.2 −

3.2 2.8 0.4 −

8.0 7.3 0.7 −

7.1 7.0 0.1 +5.9 6.7 0.8 −

10.1 9.6 0.5 −

7.4 7.5 0.1 −

6.7 7.0 0.3 −

7.9 7.9 0.0 −

4.5 4.7 0.2 −

Table 2-1. Clinical outcome and MEP monitoring

MEP monitoringCase MMT score TumorNo. Intensity Amplitude (μV) resection

Preop Postop (mA)Control Final (%)

Group A1 5 5 18.0 0.60 0.50 (83) total2 5 5 12.0 0.50 0.90 (180) total3 5 5 13.0 0.50 0.50 (100) total4 5 5 10.0 0.20 0.40 (200) subtotal5 5 5 17.5 0.30 0.40 (133) partial6 5 5 10.0 1.20 0.90 (75) subtotal7 5 5 13.0 0.70 0.87 (124) gross total8 5 2 12.0 0.10 0.0 (0) total9 5 5 17.0 0.48 0.23 (48) subtotal

10 5 5 7.0 5.62 3.35 (60) subtotal11 5 5 18.5 0.11 0.11 (100) subtotal12 5 5 12.0 0.69 0.46 (67) subtotal13 5 5 10.0 0.81 0.75 (93) gross total14 4 4 16.0 0.094 0.082 (87) partial15 4 3 20.0 0.09 0.0058 (6) partial16 5 5 12.0 3.3 5.5 (167) subtotal17 5 5 8.8 1.6 1.6 (100) subtotal18 5 5 12.0 1.0 0.64 (64) −

19 5 5 9.0 2.3 2.19 (95) −

20 5 5 15.0 0.69 0.57 (83) −

21 5 5 11.5 1.4 0.67 (48) −

22 5 5 7.7 2.8 1.84 (66) −

23 5 5 8.0 0.84 0.96 (114) −

24 5 5 21.0 0.10 0.11 (110) −

25 5 5 10.0 0.71 0.51 (72) −

26 5 5 15.0 0.199 0.178 (89) −

27 5 5 12.5 2.19 1.85 (84) −

28 5 5 19.8 0.137 0.118 (86) −

29 5 5 14.0 0.274 0.101 (37) −

30 5 5 16.0 0.51 0.55 (108) −

31 5 5 25.0 0.21 0.19 (90) −

32 5 5 11.0 3.04 3.33 (110) −

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Table 2-2. Clinical outcome and MEP monitoring

MEP monitoringCase MMT score TumorNo. Intensity Amplitude (μV) resection

Preop Postop (mA)Control Final (%)

Group B33 4 2 8.0 0.3 0.2 (67) subtotal34 5 5 15.0 3.1 1.5 (48) subtotal35 3 4 28.0 1.6 1.6 (100) gross total36 5 4 8.0 1.0 0.6 (60) gross total37 4 4 12.0 0.04 0.03 (43) gross total38 4 4 15.0 0.74 0.25 (34) gross total39 5 5 7.0 2.0 1.2 (60) partial40 5 5 13.0 0.02 0.02 (100) subtotal41 5 3 17.0 0.3 0.2 (67) total42 5 5 8.0 0.7 1.0 (143) gross total43 4 5 12.0 0.4 0.3 (75) gross total44 5 5 7.0 1.3 1.3 (100) gross total45 3 3 10.0 0.3 0.5 (167) gross total46 4 4 15.0 0.03 0.04 (133) partial47 5 5 8.0 1.4 0.69 (49) gross total48 4 4 10.0 1.15 1.47 (128) gross total49 5 5 11.0 1.48 1.02 (69) subtotal50 5 5 10.0 0.19 0.26 (137) gross total51 5 5 9.0 4.6 5.4 (117) gross total52 4 4 25.0 0.073 0.074 (101) total53 4 4 7.5 1.37 1.03 (75) subtotal54 5 5 13.7 0.74 0.8 (108) subtotal55 3 3 5.0 1.83 0.57 (31) gross total

Group C56 5 5 8.0 0.5 0.6 (120) subtotal57 5 5 4.0 0.9 0.6 (67) gross total58 4 5 10.0 0.07 0.1 (143) subtotal59 4 4 9.0 0.5 0.5 (100) gross total60 5 5 10.0 0.4 0.5 (125) subtotal61 5 5 14.0 7.8 8.4 (108) gross total62 5 5 11.0 0.3 0.6 (108) gross total63 5 5 9.0 0.27 0.35 (130) subtotal64 5 5 10.0 0.49 1.23 (251) subtotal65 5 5 6.0 2.6 2.4 (92) −

MEP, motor evoked potential; MMT, manual muscle testing

Table 3. Summary of SEP, MT, and MR imaging findings

Stimulus intensity forLatency of P20 Amplitude of P20 MT

Group for MEP monitoring T2 high (%)(mean ± SD, ms) (mean ± SD, μV) (mean ± SD, mA)

(mean ± SD, mA)

A 21.1 ± 1.3 33.9 ± 32.3 10.1 ± 3.8 (anodal) 13.6 ± 4.3 3/32 (9.3)B 20.9 ± 1.6 51.9 ± 40.4 8.4 ± 5.7 (cathodal) 12.1 ± 5.7 15/23 (65.2)**

6.6 ± 1.9 (anodal)/C 22.5 ± 1.9 84.2 ± 45.6* 9.1 ± 2.6 1/10 (10)

6.5 ± 1.9 (cathodal)

SEP, somatosensory evoked potential; MT, motor threshold; MR, magnetic resonance; SD, standard deviation*P < 0.05 compared with Group A or B; **P < 0.001 compared with Group A or C

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Figure 1. Scatter plot showing the relationship between the amplitude of P20 and the minimum MT.A statistically significant negative correlation is shown (Pearson's correlation coefficient, -0.616).

at the left postcentral gyrus with marked edema involvingthe precentral knob (Figure 2A, B). Intraoperative cortical

SEP recordings showed N20-P20 phase reversal andminimum MT was 9.0 mA with cathodal stimulation atelectrode No. 7 compared to more than 15.0 mA withanodal stimulation (Figure 3A). Continuous recordingof MEPs evoked by cathodal stimulation at 15.0 mAcould be maintained until completion of tumor resection(Figure 3B). His motor function was preserved aftersurgery. Postoperative MR imaging demonstrated grosstotal resection of the tumor (Figure 2C).

Discussion

Clinical importance of lower intensity cathodalstimulationThe present study found that cathodal stimulation inducedMEPs at significantly lower stimulus intensity than anodalstimulation in about one third of our patient population.In addition, MR imaging showed hyperintensityextending to the precentral knob in many of these patients.These findings are important because excessive intensityof anodal stimulation is sometimes required to obtainMEPs during operation. Unwanted body movements

induced by the spread of such intensive stimulation caninterfere with fine microsurgical manipulation.2

Repetitive stimulation for long periods as well as singlehigh current intensity stimulus causing insults such asexcessive charge density per phase may also cause neuraldamage.4,5 Therefore, we recommend that stimulusintensity for intraoperative MEP monitoring should beas low as possible.

Regarding the clinical outcome, the final MEPamplitude was reduced to less than 50% of the controlwithout motor hypofunction in several cases in bothGroups A and B. Postoperative motor function was finallyassessed 3 months after surgery. In the event of immediateparesis occurring, these patients fully regained theirmuscle power up to the preoperative conditions. Onepossible reason is that damage to the cortical gray mattermay not lead to axonal but preferentially to interneuronaldysfunction, resulting in transient motor paresis.1

Neurophysiological basis of cortical stimulation ofpyramidal tract neuronsStimulation of the primary motor cortex elicits excitatoryoutflow down to the spinal cord via the pyramidal tract.Descending volleys were recorded at both the ipsilateral

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Figure 2. Case 38. (A) Two consecutive slices of preoperative T1-weighted MR images withcontrast medium showing a ring-enhanced mass located in the left postcentral gyrus adjacentto the precentral knob. (B) T2-weighted MR images revealing marked peritumoral edemainvolving the precentral knob. (C) Postoperative T1-weighted MR images indicating grosstotal removal of the enhanced mass. Arrows indicate the central sulcus in each image.

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Figure 3. Case 38. (A) Intraoperative recording of cortical SEPs showing N20-P20 phase reversal between odd- and even-numberedelectrodes. The minimum MT is obtained by cathodal stimulation at electrode No. 7. (B) Continuous MEP recording showing the MEPsare preserved until the end of tumor resection, although the amplitude of the final recording was 34% of that of the control.

Figure 4. Schematic diagram of excitation of the pyramidal tract neurons by corticalstimulation. (A) The pyramidal tract neurons are oriented vertically to the cortical surface sothat positive current enters the deep apical dendrites and exits with depolarization at the axonhillock or the initial segment under normal conditions. (B) Assumed mechanism of excitationof the pyramidal tract neurons by cathodal stimulation via alternative current flow and/or theinterneurons in the precentral gyrus deformed by brain edema under pathological conditions.

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medullary pyramid and the contralateral corticospinaltract after electrical stimulation to the cortical surface ofthe primary motor area in animal studies.8,9 D wavesappeared at lower anodal than cathodal stimulusintensities.10,11 The pyramidal tract neurons are orientedvertically to the cortical surface so that positive currentfrom the anodal electrodes on the cortical surface entersthe deep apical dendrites and exits with depolarization atthe axon hillock or the initial segment (Figure 4A).8,12,13

D waves can be elicited by direct axonal excitation, sothey can be stably recorded in humans under generalanesthesia14 and with concomitant cortical depression.8,9

Anodal stimulation elicits direct excitation of axons ofthe pyramidal tract neurons (D waves), whereas cathodalstimulation induces indirect excitation of the pyramidaltract neurons mediated by interneurons (I waves).8,10

Possible inputs to the pyramidal tract, which is responsiblefor the generation of I waves, include corticocortical orintrinsic axons, and superficial tangential axons orcollateral axons of the pyramidal tract.8,15

Why is the MT lower with cathodal than anodalstimulation?The exact mechanism causing lower cathodal than anodalMT in Group B remains unknown. However, theelectrophysiological properties of the pyramidal tractneurons are likely affected by the presence of abnormalneighboring structures such as tumor and peritumoraledema, because the anodal MT is normally lower inpatients with a cerebral aneurysm who do not demonstratesuch structural changes. Peritumoral edema and/or tumorinfiltration extending to the precentral knob, which maycause structural deformity, were present in a significantnumber of Group B patients. Such pathologicalconditions may induce anatomophysiological changesin the passage of stimulus current flow to the pyramidaltract neurons and/or in the interneurons (Figure 4B).8,10,11

Plasticity of the motor cortex is known in patientswith gliomas located in the precentral region.16-18 Cervicalmyelopathy causing impairment of the pyramidal tractcan also induce functional cortical reorganization.19

Interneuron networks may be very important in motorcortical plasticity.20

Inappropriate location of the stimulation electrodesremains a possibility. Under such conditions, anodalstimulation cannot depolarize the pyramidal tract neuronsdirectly, whereas cathodal stimulation may causeexcitation via the corticocortical or superficial tangentialfibers in an area adjacent to the motor hand area.

Cathodal stimulation can allow intraoperative MEPmonitoring at lower stimulus intensity in some patients

with brain tumors. Further investigations to determinewhether the MT is lower with cathodal or anodalstimulation are warranted, especially if anodal stimulationrequires comparatively high intensities. MR imagingfindings of peritumoral edema extending to the precentralknob may be indicative of appropriate cases for cathodalstimulation.

Acknowledgement

We thank Ritsuko Hanajima, M.D., Ph.D., of theDepartment of Neurology, Kitasato University Schoolof Medicine, for many helpful comments onneurophysiological considerations.

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Cathodal stimulation for MEP monitoring