Higher success rate with transcranial electrical stimulation of motor-evoked potentials using constant-voltage stimulation compared with constant-current stimulation in patients undergoing spinal surgery

Higher success rate with transcranial electrical stimulation of motor-evoked potentials using constant-voltage stimulation compared with constant-current stimulation in patients undergoing spinal surgery

Accepted Manuscript Title: Higher success rate with transcranial electrical stimulation of motor evoked potentials using constant-voltage stimulation ...

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Accepted Manuscript Title: Higher success rate with transcranial electrical stimulation of motor evoked potentials using constant-voltage stimulation compared with constantcurrent stimulation in patients undergoing spinal surgery Author: Hideki Shigematsu, Masahiko Kawaguchi, Hironobu Hayashi, Tsunenori Takatani, Eiichiro Iwata, Masato Tanaka, Akinori Okuda, Yasuhiko Morimoto, Keisuke Masuda, Yuu Tanaka, Yasuhito Tanaka PII: DOI: Reference:

S1529-9430(17)30195-X http://dx.doi.org/doi: 10.1016/j.spinee.2017.05.004 SPINEE 57315

To appear in:

The Spine Journal

Received date: Revised date: Accepted date:

18-10-2016 11-3-2017 2-5-2017

Please cite this article as: Hideki Shigematsu, Masahiko Kawaguchi, Hironobu Hayashi, Tsunenori Takatani, Eiichiro Iwata, Masato Tanaka, Akinori Okuda, Yasuhiko Morimoto, Keisuke Masuda, Yuu Tanaka, Yasuhito Tanaka, Higher success rate with transcranial electrical stimulation of motor evoked potentials using constant-voltage stimulation compared with constant-current stimulation in patients undergoing spinal surgery, The Spine Journal (2017), http://dx.doi.org/doi: 10.1016/j.spinee.2017.05.004. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Higher success rate with transcranial electrical stimulation of motor evoked potentials

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using constant-voltage stimulation compared with constant-current stimulation in patients

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undergoing spinal surgery

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Hideki Shigematsua*, Masahiko Kawaguchib, Hironobu Hayashib, Tsunenori Takatanic, Eiichiro

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Iwataa, Masato Tanakaa, Akinori Okudaa, Yasuhiko Morimotoa, Keisuke Masudaa, Yuu Tanakab,

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Yasuhito Tanakaa

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a

Department of Orthopaedic Surgery, Nara Medical University, 840 Shijo-cho Kashihara City,

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Nara 6348522, Japan

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b

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6348522, Japan

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c

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Nara 6348522, Japan

Department of Anesthesiology, Nara Medical University, 840 Shijo-cho Kashihara City, Nara

Division of Central Clinical Laboratory, Nara Medical University, 840 Shijo-cho Kashihara City,

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*Corresponding author:

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Hideki Shigematsu

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Department of Orthopaedic Surgery, Nara Medical University

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840 Shijo-cho Kashihara City, Nara 6348522, Japan

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Tel.: +81-74422-3051; Fax: +81-74425-6449; E-mail address: [email protected]

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Conflicts of Interest and Sources of Funding: None declared.

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Abstract

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BACKGROUND CONTEXT: During spine surgery, the spinal cord is electrophysiologically

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monitored via transcranial electrical stimulation motor evoked potentials (TES-MEP) to prevent

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injury. TES-MEP involves the use of either constant-current or constant-voltage stimulation;

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however, there are few comparative data available regarding their ability to adequately elicit

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compound motor action potentials (CMAPs). We hypothesized that the success rates of

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TES-MEP recordings would be similar between constant-current and constant-voltage

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stimulation in patients undergoing spine surgery.

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PURPOSE: To compare the success rates of TES-MEP recordings between constant-current

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and constant-voltage stimulation.

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STUDY DESIGN: Prospective.

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PATIENT SAMPLE: Data from 100 patients undergoing spinal surgery at the cervical,

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thoracic, or lumbar levels were analyzed.

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OUTCOME MEASURES: The success rates of the TES-MEP recordings from each muscle

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were examined.

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METHODS: TES with constant-current and constant-voltage stimulation at the C3 and C4

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electrode positions (international “10–20” system) were applied to each patient. CMAPs were

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bilaterally recorded from the abductor pollicis brevis (APB), deltoid (Del), abductor hallucis

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(AH), tibialis anterior (TA), gastrocnemius (GC), and quadriceps (Quad) muscles.

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RESULTS: The success rates of the TES-MEP recordings from the right Del, right APB,

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bilateral Quad, right TA, right GC, and bilateral AH muscles were significantly higher using

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constant-voltage stimulation than they were with constant-current stimulation. The overall

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success rates with constant-voltage and constant-current stimulation were 86.3% and 68.8%,

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respectively (risk ratio 1.25[95% CI: 1.20–1.31]).

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CONCLUSIONS: The success rates of TES-MEP recordings were higher using

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constant-voltage stimulation compared with constant-current stimulation in patients undergoing

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spinal surgery.

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LEVEL OF EVIDENCE: 2

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KEY WORDS: transcranial electrical stimulation, compound motor action potential, motor

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evoked potential, constant current, constant voltage, risk ratio

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Abbreviations:

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AH: Abductor hallucis

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APB: Abductor pollicis brevis

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CMAPs: Compound muscle action potentials

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Del: Deltoid

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GC: Gastrocnemius

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Quad: Quadriceps

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RR: Risk ratio 3 Page 3 of 22

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TA: Tibialis anterior

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TES-MEP: Transcranial electrical stimulation of motor-evoked potentials

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Introduction

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Transcranial electrical stimulation of motor-evoked potentials (TES-MEP) is widely used for

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intra-operative spinal cord monitoring when risks to spinal cord health are possible during

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surgery. By recording compound muscle action potentials (CMAPs) from upper- and lower-limb

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muscles, TES-MEP can be used to monitor motor function during such surgeries [1-4].

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Measuring CMAPs after transcranial brain stimulation is minimally invasive, and can reflect

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motor function in the lateral corticospinal tracts, but only represent a small fraction of the

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overall number of motor units innervating a particular muscle [5]. In addition to supporting the

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functions of motor-related tracts, the functions of the anterior horn cells and spinal nerve roots

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of the segment innervating the target muscle can be evaluated by monitoring CMAPs. To

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optimize the detection of motor deficits, the number of channels used for CMAP monitoring

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must be maximized. Ito et al. reported that at least eight channels are required for intraoperative

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spinal cord monitoring [6]. In other words, the successful intraoperative detection of CMAPs is

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critical for preventing motor pathway damage during spine surgery.

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To date, two types of stimulators have been used for TES-MEP, namely, constant-voltage

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stimulators and constant-current stimulators. Constant-voltage stimulators adjust the current to

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maintain the voltage, while constant-current stimulators adjust the voltage to maintain the

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current. According to Macdonald et al., constant-voltage stimulators are the most commonly

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used type for TES-MEP for historical and regulatory reasons [7]. Although Hausmann et al. [8]

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compared the two devices in a small population, no previous reports have assessed whether one

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method is superior to the other for intra-operative monitoring, i.e., for detecting CMAPs in a

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large population. Thus, the present study was performed to clarify whether one type of

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stimulator had potential superiority over the other for detecting CMAPs during intra-operative

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spinal cord monitoring via TES-MEP. We assessed the relative success of each stimulator in

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detecting CMAPs in the same patient group (i.e., within subjects), and each stimulator’s 5 Page 5 of 22

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effectiveness within different muscles across the upper and lower limbs.

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Materials and methods

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This prospective, within-subjects study was approved by the local institutional review board. All

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patients provided informed written consent in accordance with ethical standards.

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Subjects

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The potential subject pool consisted of 258 patients who underwent elective spine and spinal

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cord surgery between July 2014 and April 2016, in which TES-MEP was used to monitor motor

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function. Of these 258 patients, 141 declined to participate. Both constant-voltage and

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constant-current stimulators were used in 117 patients. However, 17 patients did not have

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sufficient clinical data; thus, the study ultimately included 100 patients (Figure 1). The 43 male

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and 51 female patients ranged in age from 14 to 85 years (mean, 62 years). Patients had been

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diagnosed with cervical spinal stenosis (n = 27), cervical ossification of the posterior

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longitudinal ligament (n = 3), cervical tumor (n = 2), lumbar canal stenosis (n = 35), lumbar

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spondylolisthesis (n = 5), lumbar spinal tumor (n = 3), thoracic tumor (n = 7), scoliosis (n = 3),

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or other spinal disorders (n = 15). Preoperative mild to severe motor weakness (manual muscle

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test: 0−3) from any muscle was present in 21 (21%) of the 100 patients.

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Anesthesia

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To minimize the suppressive effects of the anesthetic agents and neuromuscular blockades on

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MEP waveforms, anesthesia was standardized for all patients as follows. No medication was

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administered before anesthesia. Anesthesia was induced using 2–4 μg/kg of fentanyl, 0.25–0.5

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μg/TT of remifentanil, and 3.0–5.0 μg/mL of propofol through a target-controlled infusion pump

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(TE-371; Terumo, Tokyo, Japan). After induction, tracheal intubation was facilitated using 0.6

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mg/kg of rocuronium. Anesthesia was maintained with a regimen of propofol (2.0–3.0 μg/mL), 6 Page 6 of 22

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fentanyl, and remifentanil (0.20–0.5 μg/[kg·min]c) using a target-controlled infusion pump. The

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depth of anesthesia was adjusted to maintain the bispectral index within the range of 40–60. No

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additional neuromuscular blockades were administrated after tracheal intubation to avoid

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pharmacological reduction and disappearance of the MEP waveforms. Sugammadex was

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administrated to reverse the profound residual neuromuscular blockade induced by rocuronium

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only if the ratio of the fourth response to the first response in the train of four monitoring at the

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timing of control MEP recordings did not return to at least 0.80. After the trachea was intubated,

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the lungs were ventilated mechanically to maintain the level of partial pressure of end-tidal

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carbon dioxide between 30 and 40 mmHg. A mixture of air and oxygen was administered. The

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rectal temperature was maintained between 35.5° and 37.0° C.

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Stimulators

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The parameters used for each stimulation type are summarized in Table 1. The constant-voltage

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stimulator was an SEN-4100 (Nihon Koden, Tokyo, Japan), and the constant-current stimulator

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was an MS-120B (Nihon Koden, Tokyo, Japan). Both constant-voltage and constant-current

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stimulators were used in all of the patients. In a preliminary study, the authors determined that a

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2 min interval after MEP recording did not affect subsequent MEP responses; therefore, the

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interval of MEP recordings was set at more than 2 min. Monophasic stimulation was used,

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which was delivered through right anode and left cathode stimulating electrodes (Figure 2).

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Briefly, a train of five stimulating pulses was delivered at 500 Hz (2 ms interstimulus intervals).

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Stimulating electrodes consisted of a pair of 14.5 mm silver-plated disc electrodes at the C3

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(cathode) and C4 (anode) locations of the international “10–20” system for the scalp (Figure 3),

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and were affixed using conductive paste. The intensity of transcranial stimulation was determined

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at the outset of TES-MEP recording and based on previously published data. Accordingly, our

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devices were set to deliver maximum stimulus in each case (500 V and 200 mA), which

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corresponded to the maximum stimulation setting on either device. CMAPs were recorded on the 7 Page 7 of 22

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first trial at baseline, after the disappearance of the effect of muscle relaxation.

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Recording of CMAPs

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CMAPs were bilaterally recorded from the skin over the abductor pollicis brevis (APB), deltoid

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(Del), abductor hallucis (AH), tibialis anterior (TA), gastrocnemius (GC), and quadriceps

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(Quad) muscles. A ground electrode was placed on the left or right arm proximal to the elbow.

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An intra-operative TES-MEP measurement system (Neuromaster MEE1232; Nihon Koden,

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Tokyo, Japan) was used to collect CMAP data.

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Study protocol

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Both constant-voltage and constant-current stimulations were used during the operation in each

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patient. CMAP recordings were initiated when the effects of the muscle relaxant that was

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administered during anesthetic induction had worn off (i.e., train of four >80%).

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TES-MEP recording was considered to be successful when the recorded amplitude of CMAPs

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was > 50 µV [9]. Once the recordings were completed, the success rates of the constant-voltage

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and constant-current stimulations were compared for each individual muscle, as well as for the

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upper- and lower-limb muscle groups, and for the overall set of data for each stimulator. The

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amplitudes of the CMAPs obtained using constant-voltage and constant-current stimulation

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were also compared.

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Statistical analysis

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All data were collected, and statistical analyses were performed using SPSS version 17.0 (IBM,

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Chicago, IL). The success rates of the baseline recordings between constant-voltage and

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constant-current stimulation for all analyzed muscles were compared using a risk ratio (RR),

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while the wave amplitudes for each muscle were compared using a Wilcoxon signed-rank test. 8 Page 8 of 22

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The threshold of statistical significance was p < 0.05.

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Results

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A constant-voltage stimulation of 500 V and constant-current stimulation of 200 mA was used.

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The number of muscles analyzed successfully per location during each type of stimulation is

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presented in Table 2, while Table 3 presents the total number of muscles measured for the upper-

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and lower-limb groups, as well as a summary for the entire study.

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Success rates for each stimulation type per individual muscle

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In terms of individual muscle locations, significantly higher success rates were found for

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constant-voltage stimulation than for constant-current stimulation at the right Del, right APB,

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bilateral Quad, right TA, right GC, and bilateral AH (Table 2). As shown in Table 3,

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constant-voltage stimulation was more successful than constant-current stimulation in the upper-

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and lower-limb muscle groups, and in the overall recorded data. Based on the overall recorded

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data for the two stimulation conditions, constant-voltage stimulation was better than

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constant-current stimulation for detecting CMAPs >50 µV (RR 1.25 [95% CI: 1.20–1.31]). The

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effectiveness of constant-current stimulation was not significantly greater than constant-voltage

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stimulation in any of the cases. Furthermore, no statistically significant differences were found

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between the right and left sides for constant-voltage stimulation. However, statistically

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significant differences were noted between the right and left sides for constant-current

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stimulation, except in the Del (Table 4).

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Wave amplitudes per individual muscle

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The amplitudes of the upper-limb muscles are shown in Figure 4, while the amplitudes of the

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lower-limb muscles are shown in Figure 5. Although the amplitudes varied widely between

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individual muscles for any given patient, they were consistently higher for most of the 9 Page 9 of 22

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individual muscles when using constant-voltage stimulation compared with constant-current

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stimulation. The only amplitudes that were not consistently higher with constant-voltage

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stimulation were those from the left Del and left APB (Table 5).

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Illustrative case

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A 57-year-old man had a metastatic tumor at the level of the cervical spine. He did not exhibit

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any neurological deficits before surgery. Constant-voltage stimulation demonstrated a high

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success rate, wherein the amplitudes of the CMAPs were >50 µV (Figure 6a, b).

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Discussion

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Many previous reports have indicated the importance of spinal monitoring during surgery, with

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TES-MEP being regarded as the “gold standard” [10-13]. This is because TES-MEP is relatively

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non-invasive and can be performed by recording CMAPs from many different muscles in the

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upper or lower limbs. Another advantage of TES-MEP is that the laterality can be analyzed.

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However, CMAPs can be impeded or even eliminated by disorders that require surgical

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intervention, such as cord compression or tumors, rendering some muscles incapable of being

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monitored clinically. As mentioned above, Ito et al. suggested that at least eight channels should

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be monitored during spinal cord surgery to detect postoperative motor deficits [6] . Given the

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potential lack of recordable muscles in patients with severe spinal cord problems, the successful

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intra-operative recording of CMAPs is very important for a reliable prognosis for postoperative

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recovery.

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Macdonald et al reported that the stimulating current depends on resistance, which varies with

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multiple factors and, furthermore, that the stimulating current may change during surgery, even

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with constant-voltage stimulators. Consequently, a delivered current read out is desirable [7, 14].

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In contrast, constant-current stimulators adjust the voltage to deliver a specified current

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independent of resistance (within compliance limits). 10 Page 10 of 22

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Regarding the differences between stimulation types, we found that constant-voltage stimulation

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was at least modestly superior to constant-current stimulation with regard to successfully

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producing detectable CMAPs (RR 1.25 [95% CI: 1.20–1.31]). The success rate when using

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constant-voltage stimulation was significantly higher when analyzing the muscles as a single

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group or when the muscles were grouped according to location (significance in either the upper-

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or lower-limb muscles). These results are supported by the mean wave amplitude analyses

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(Figures 4 and 5), which demonstrated that the amplitudes elicited when using constant-voltage

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stimulation to record the CMAPs from the right upper-limb muscles and all of the lower-limb

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muscles were consistently higher than those elicited when using constant-current stimulation.

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The reason why the left upper-limb muscles appeared to be less affected by the stimulation may

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be that transcranial stimulation predominantly stimulates the brain on the anode side, thus

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evoking large MEPs on the contralateral side [4, 15]. In this study, we used monophasic

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stimulation, with the anode located on the right side. Therefore, large MEPs were likely evoked

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on the left side. We believe that the lack of significant differences between constant-current and

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constant-voltage stimulation on the left side was related to this phenomenon. Interestingly, no

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significant differences were noted between the right and left sides for constant-voltage

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stimulation. Thus, the constant-voltage stimulation appeared to stimulate the upper and lower

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limbs bilaterally in this study.

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Our study had several limitations. First, our cases included several types of spinal disorders,

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which were distributed over the entire spinal cord. Although this may broaden the applicability

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of constant-voltage and constant current stimulation in the future, it incorporates several

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potential confounding variables that may have reduced our ability to identify differences

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between the techniques. Second, the number of cases was limited, mostly owing to patient

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preference in our potential subject pool. Third, this study analyzed only two variables: success

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rate and wave amplitude. Although it is potentially important to evaluate the stimulation type in

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terms of the degree to which stimulation reached the pyramidal tract, it was not clinically 11 Page 11 of 22

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feasible here. Fourth, we used the maximum stimulation settings of our devices in this study.

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Although our results showed that constant-voltage stimulation performed better than

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constant-current stimulation in terms of successfully evoking CMAPs, it is conceivable that

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constant-voltage stimulation was simply more supramaximal than the constant current

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stimulation. Fifth, we placed the stimulating electrodes on C3 and C4 according to the

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international “10–20” system, but did not determine whether placing the electrodes at different

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stimulating montages or locations transcranially would generate different results. Sixth, voltage

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reflects the potential difference in charge, and is the most relevant parameter for stimulation [7];

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however, we did not compare charges between the two groups. Finally, as mentioned above,

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constant-voltage stimulation appeared to stimulate both sides of the upper and lower limbs.

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However, currently, our data cannot logically explain this phenomenon; hence, additional

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studies are needed.

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Conclusion

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When using TES-MEP to monitor the spinal cord during surgery, transcranial stimulation can be

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achieved through either constant-voltage or constant-current stimulation. Here, we found that in

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many instances, constant-voltage stimulation performed better than constant-current stimulation

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in terms of successfully evoking CMAPs. Based on our results, the use of constant-voltage

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stimulation may be preferable to constant-current stimulation, especially in cases in which

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CMAP expression may be compromised by the spinal disorder being treated.

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Acknowledgements: The authors thank Junko Kato, Kazuya Morimoto, Kiyomi Mameda,

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Ryohei Mizobata, and Aya Nakamori for their technical assistance with TES-MEP.

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References [1] Machida M, Weinstein SL, Yamada T, Kimura J, Itagaki T, Usui T. Monitoring of motor

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action potentials after stimulation of the spinal cord. J Bone Joint Surg Am

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1988;70:911−8.

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[2] Mochida K, Shinomiya K, Komori H, Furuya K. A new method of multisegment motor

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pathway monitoring using muscle potentials after train spinal stimulation. Spine (Phila

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Pa 1976) 1995;20:2240−6.

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[3] Zentner J. Noninvasive motor evoked potential monitoring during neurosurgical operations on the spinal cord. Neurosurgery 1989;24:709−12. [4] Jones SJ, Harrison R, Koh KF, Mendoza N, Crockard HA. Motor evoked potential

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monitoring during spinal surgery: responses of distal limb muscles to transcranial

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cortical stimulation with pulse trains. Electroencephalogr Clin Neurophysiol

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1996;100:375−83.

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[5] Leppanen RE. Intraoperative monitoring of segmental spinal nerve root function with

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free-run and electrically-triggered electromyography and spinal cord function with

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reflexes and F-responses. A position statement by the American Society of

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Neurophysiological Monitoring. J Clin Monitor Comput 2005;19:437−61.

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[6] Ito Z, Matsuyama Y, Shinomiya K, Ando M, Kawabata S, Kanchiku T, et al. Usefulness

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of multi-channels in intraoperative spinal cord monitoring: multi-center study by the

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Monitoring Committee of the Japanese Society for Spine Surgery and Related Research.

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Eur Spine J 2013;22:1891−6.

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[7] Macdonald DB, Skinner S, Shils J, Yingling C. Intraoperative motor evoked potential

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monitoring – a position statement by the American Society of Neurophysiological

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Monitoring. Clin Neurophysiol 2013;124:2291−316.

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[8] Hausmann ON, Min K, Boos N, Ruetsch YA, Erni T, Curt A. Transcranial electrical

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stimulation: significance of fast versus slow charge delivery for intra-operative 13 Page 13 of 22

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monitoring. Clin Neurophysiol 2002;113:1532−5. [9] Lyon R, Feiner J, Lieberman JA. Progressive suppression of motor evoked potentials

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during general anesthesia: the phenomenon of "anesthetic fade." J Neurosurg

4

Anesthesiol 2005;17:13−9.

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[10] Calancie B, Harris W, Brindle GF, Green BA, Landy HJ. Threshold-level repetitive

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transcranial electrical stimulation for intraoperative monitoring of central motor

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conduction. J Neurosurg 2001;95:161−8.

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[11] Macdonald DB, Stigsby B, Al Homoud I, Abalkhail T, Mokeem A. Utility of motor

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evoked potentials for intraoperative nerve root monitoring. J Clin Neurophysiol

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2012;29:118−25.

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[12] Langeloo DD, Lelivelt A, Louis Journee H, Slappendel R, de Kleuver M. Transcranial

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electrical motor-evoked potential monitoring during surgery for spinal deformity: a

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study of 145 patients. Spine (Phila Pa 1976) 2003;28:1043−50.

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[13] Nakagawa Y, Tamaki T, Yamada H, Nishiura H. Discrepancy between decreases in the

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amplitude of compound muscle action potential and loss of motor function caused by

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ischemic and compressive insults to the spinal cord. J Orthop Sci 2002;7:102−10.

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[14] Macdonald DB. Intraoperative motor evoked potential monitoring: overview and

18 19

update. Journal of clinical monitoring and computing. 2006;20:347−77. [15] Pechstein U, Cedzich C, Nadstawek J, Schramm J. Transcranial high-frequency

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repetitive electrical stimulation for recording myogenic motor evoked potentials with

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the patient under general anesthesia. Neurosurgery 1996;39:335−44.

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14 Page 14 of 22

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Figure 1. Flow diagram of patient enrollment and inclusion. The initial pool consisted of 258

3

patients; of these, data for the study were analyzed from a final group of 100 individuals.

4 5

Figure 2. The stimulation condition and muscles recorded during transcranial electrical

6

stimulation of motor evoked potentials for monophasic stimulation. AH: abductor hallucis,

7

APB: abductor pollicis brevis, Del: deltoid, GC: gastrocnemius, ISI: inter-stimulus interval,

8

Quad: quadriceps, TA: tibialis anterior.

9 10

Figure 3. Anatomical locations according to the international 10–20 system.

11 12

Figure 4. The compound motor action potential wave amplitudes of the tested upper-limb

13

muscles. The abductor pollicis brevis (APB) and deltoid (Del) were tested. Statistically

14

significant differences were identified between the two types of stimulation in the right (Rt)

15

APB and Rt Del. Significant differences between the stimulation types are denoted as *p < 0.01.

16

Lt: left.

17 18

Figure 5. The compound motor action potential wave amplitudes of the tested lower-limb

19

muscles. The quadriceps (Quad), tibialis anterior (TA), gastrocnemius (GC), and abductor

20

hallucis (AH) muscles were analyzed. Significant differences between stimulation types were

21

found in all muscles. Significant differences between stimulation types are denoted as *p < 0.01.

22

Rt: right, Lt: left.

23 24

Figure 6. The wave images of compound muscle action potentials (CMAPs) obtained via

25

transcranial electrical stimulation of motor evoked potentials from a 57-year-old man. a:

26

CMAPs obtained using constant-current stimulation. b: CMAPs obtained using constant-voltage 15 Page 15 of 22

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stimulation. Rt: right, Lt: left, Quad: quadriceps, TA: tibialis anterior, GC: gastrocnemius, AH:

2

abductor hallucis, APB: abductor pollicis brevis, Del: deltoid

3

16 Page 16 of 22

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Table 1. The condition of the stimulation in our hospital

constant Current

constant Voltage

Stimulus count

5

5

number of train

1

1

Stimulus interval

2 msec

2 msec

Stimulus rate

500 Hz

500 Hz

Record time

100-200 msec

100-200 msec

Stimulus duration time

0.2 msec

50 μsec

Filter

2-3k HZ

2-3k Hz

Stimulus voltage

200 mA

500 V

3

17 Page 17 of 22

1 2

Table 2: The number of successful recordings and the associated success rates for each muscle during each type of stimulation Constant-current stimulation Muscle

Laterality

Constant-voltage stimulation

Number of cases Number of successes

Success rate (%)

Number of successes

Success rate (%)

Right

100

72

72.0

91

91.0

Left

100

81

81.0

88

88.0

Right

100

71

71.0

95

95.0

Left

100

93

93.0

92

92.0

Right

100

35

35.0

65

65.0

Left

100

55

55.0

69

69.0

Right

100

54

54.0

90

90.0

Del

APB

Quad

TA

18 Page 18 of 22

Left

100

79

79.0

87

87.0

Right

100

47

47.0

82

82.0

Left

100

73

73.0

84

84.0

Right

100

75

75.0

95

95.0

Left

100

90

90.0

98

98.0

GC

AH

1

Del: deltoid, APB: abductor pollicis brevis, Quad: quadriceps, TA: tibialis anterior, GC: gastrocnemius, AH: abductor hallucis

2

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Table 3: The number of successful recordings and the associated success rates for the upper- and lower-limb muscles during each type of stimulation Constant-current stimulation Muscle group

Constant-voltage stimulation

Number of cases Number of successes

Success rate (%)

Number of successes

Success rate (%)

Upper limbs

400

317

79.3

366

91.5

Lower limbs

800

508

63.5

670

83.8

Total

1200

825

68.8

1036

86.3

3

Upper limbs = deltoid + abductor pollicis brevis muscles

4

Lower limbs = quadriceps + tibialis anterior + gastrocnemius + abductor hallucis muscles

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20 Page 20 of 22

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Table 4: Comparison of the success rates for each type of stimulation between the right and left

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sides Constant-voltage stimulation Muscle

Laterality Success rate (%)

Success rate (%)

Right

72

91

Left

81

88

Right

71

95

Left

93

92

Right

35

65

Left

55

69

Right

54

90

Left

79

87

Right

47

82

Left

73

84

Right

75

95

Left

90

98

Del

APB

Quad

TA

GC

AH

3

Del: deltoid, APB: abductor pollicis brevis, Quad: quadriceps, TA: tibialis anterior, GC:

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gastrocnemius, AH: abductor hallucis 21 Page 21 of 22

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Table 5: The amplitude of the CMAPs recorded from each muscle muscles Del APB Quad TA GC AH

3

laterality

number of cases

Rt

constant current

constant voltage

p value

Median

interquartile range

Median

interquartile range

100

170.0

[31.3, 601.5]

516.0

[165.5, 1462.5]

< 0.01

Lt

100

325.0

[100.5, 811.8]

368.5

[131.0, 837.5]

0.15

Rt

100

485.0

[22.8, 1777.5]

1220.0

[225.0, 3002.5]

< 0.01

Lt

100

1060.0

[258.8, 2685.0]

1175.0

[221.8, 2877.5]

0.98

Rt

100

9.7

[0, 145.8]

103.0

[14.2, 555.8]

< 0.01

Lt

100

71.5

[1.0, 303.8]

150.0

[26.3, 410.5]

< 0.01

Rt

100

68.5

[1.0, 390.0]

572.5

[135.3, 2295.0]

< 0.01

Lt

100

290.0

[61.0, 1470.0]

630.0

[100.0, 1720.0]

< 0.01

Rt

100

41.0

[0, 192.8]

247.5

[84.3, 868.8]

< 0.01

Lt

100

185.0

[27.3, 616.3]

340.0

[84.0, 872.5]

< 0.01

Rt

100

160.0

[35.8, 645.0]

1045.0

[352.5, 1992.5]

< 0.01

Lt

100

796.0

[201.3, 1688.5]

1120.0

[452.3, 2417.3]

< 0.01

Del: deltoid, APB: abductor pollicis brevis, Quad: quadriceps, TA: tibialis anterior, GC: gastrocnemius, AH: abductor hallucis

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