J Clin Monit Comput DOI 10.1007/s10877-014-9565-7
Augmentation of motor evoked potentials using multi-train transcranial electrical stimulation in intraoperative neurophysiologic monitoring during spinal surgery Shunji Tsutsui • Hiroshi Iwasaki • Hiroshi Yamada • Hiroshi Hashizume • Akihito Minamide • Yukihiro Nakagawa • Hideto Nishi • Munehito Yoshida
Received: 21 December 2013 / Accepted: 12 February 2014 Ó Springer Science+Business Media New York 2014
Abstract Transcranial motor evoked potentials (TcMEPs) are widely used to monitor motor function during spinal surgery. Improvements in transcranial stimulation techniques and general anesthesia have made it possible to record reliable and reproducible potentials. However, TcMEPs are much smaller in amplitude compared with compound muscle action potentials (CMAPs) evoked by maximal peripheral nerve stimulation. In this study, multi-train transcranial electrical stimulation (mtTES) was introduced to enhance TcMEPs, and the optimal setting of mt-TES was investigated. In 30 patients undergoing surgical correction of spinal deformities (4 males and 26 females with normal motor status; age range 11–75 years), TcMEPs from the abductor hallucis (AH) and quadriceps femoris (QF) were analyzed. A multipulse (train) stimulus with an individual pulse width of 0.5 ms and an inter-pulse interval of 2 ms was delivered repeatedly (2–7 times) at different rates (2, 5, and 10 Hz). TcMEP amplitudes increased with the number of train stimuli for AH, with the strongest facilitation observed at 5 Hz. The response amplitude increased 6.1 times on average compared with single-train transcranial electrical stimulation (st-TES). This trend was also observed in the QF. No adverse events (e.g., seizures, cardiac arrhythmias, scalp burns, accidental injury resulting from patient movement) were observed in any patients. Although several facilitative techniques using central or peripheral stimuli, preceding transcranial electrical stimulation, have been recently employed to augment TcMEPs during
S. Tsutsui (&) H. Iwasaki H. Yamada H. Hashizume A. Minamide Y. Nakagawa H. Nishi M. Yoshida Department of Orthopaedic Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8510, Japan e-mail: [email protected]
surgery, responses are still much smaller than CMAPs. Changing from conventional st-TES to mt-TES has potential to greatly enhance TcMEP responses. Keywords Intraoperative neurophysiologic monitoring Motor evoked potential Multi-train transcranial electrical stimulation Spinal surgery
1 Introduction It is essential to monitor motor function during spinal surgery that may damage the spinal cord or the spinal nerve roots. Transcranial motor evoked potentials (TcMEPs), which are muscle action potentials elicited by transcranial brain stimulation, have been widely used for multisegment motor pathway monitoring during surgery. Improvements in transcranial stimulation techniques and general anesthesia have made it possible to record reliable and reproducible potentials [1–5]. However, TcMEPs are much smaller in amplitude compared with compound muscle action potentials (CMAPs) evoked by maximal peripheral nerve stimulation, and vary in clinical practice, suggesting that only a limited number of spinal motor neurons innervating the target muscle are excited by the currently used transcranial stimulation techniques [6, 7]. Therefore, reliable interpretation of the critical changes in TcMEPs remains controversial [8–16]. Additionally, in our clinical experience, we have occasionally encountered false negative cases in which patients have suffered from focal postoperative segmental motor weakness mostly due to single nerve root injury, despite no significant change in TcMEP activity during surgery . In such cases, TcMEPs may not have been reliable monitors of activity in motor units damaged intraoperatively, because of radicular
J Clin Monit Comput
overlap and different dominancy of each nerve root innervating the recorded muscle [18, 19]. Recently, several facilitative techniques using central or peripheral stimuli, preceding transcranial electrical stimulation, have been employed to achieve sufficient depolarization of motor neurons and augment TcMEP responses during surgery [20–24]. In addition, it was previously reported that recurrent pulse trains at low frequency built up TcMEP responses [25–29]. In this study, the optimal setting of multiple transcranial electrical pulse trains, socalled multi-train transcranial electrical stimulation (mtTES), was systematically investigated to enhance TcMEP responses.
2 Materials and methods Thirty patients undergoing surgical correction of spinal deformities (4 males and 26 females with normal motor status; aged 11–75 years) gave written informed consent to participate in this study, which was approved by the ethical committee of Wakayama Medical University. A total intravenous anesthetic technique was employed. Anesthesia was induced with a bolus of propofol (1.5 mg/ kg), remifentanil (0.5–1.0 lg/kg), and the short-acting muscle relaxant rocuronium (0.6–0.8 mg/kg), and maintained with propofol (6–10 mg/kg/h) and remifentanil (0.25 lg/kg/min). A muscle relaxant was given only at anesthetic induction to facilitate tracheal intubation. A constant-current stimulator (MS-120B, Nihon Koden, Tokyo, Japan) was used for transcranial brain stimulation. A train of five biphasic stimuli, 0.5-ms in duration (two phases of 0.25 ms in each stimulus), was delivered with an intensity of 200 mA (maximal intensity of the stimulator used) and an inter-pulse interval of 2 ms via a pair of corkscrew electrodes (001–220; Agram, NJ, USA) symmetrically inserted into the scalp, 5 cm lateral and 2 cm forward of Cz (International 10-20 System of electrode placement), based on the method of Matsuda and Shimazu . TcMEPs were recorded from a pair of needle electrodes (NE-220B; Technomed Europe, Amerikalaan, The Netherlands) inserted in the muscle belly of the abductor hallucis (AH) and quadriceps femoris (QF). All measurements were taken before any corrective manipulation of the spine was performed after complete recovery from the effect of the muscle relaxant, which was monitored using the ‘‘Train of Four’’ technique. A multipulse (train) stimulus was delivered repeatedly (2–7 times) at different rates (2, 5, and 10 Hz), and was defined as mt-TES. The amplitudes of TcMEP responses after mt-TES were compared with those elicited by conventional single-train transcranial electrical stimulation (stTES).
Fig. 1 Augmentation of motor evoked potentials recorded from the AH muscle by mt-TES at different repetitive rates (2, 5, and 10 Hz). Each individual train consists of five biphasic pulses 0.5-ms in duration (two phases of 0.25 ms in each pulse) and a 2.0-ms interpulse interval. The number of train stimuli was changed from two to seven. st-TES single-train transcranial electrical stimulation
3 Results The mean amplitudes of the TcMEPs recorded by st-TES immediately before the measurement using mt-TES were 0.616 mV (range 0.01–2.49 mV) for AH and 0.186 mV (range 0.01–0.78 mV) for QF. TcMEP amplitudes increased with the number of train stimuli for AH, and the strongest facilitation was observed at a repetition rate of 5 Hz (Fig. 1). The response amplitude increased up to 6.1 times on average compared to st-TES (Fig. 2). This trend was also observed in the QF (Fig. 3). The response amplitude increased up to 8.0 times on average compared with st-TES (Fig. 4). No adverse events (e.g., seizures, cardiac arrhythmias, scalp burns, accidental injury resulting from patient movement) were observed in any patients.
4 Discussion The present investigation demonstrated that mt-TES is a simple and effective method to augment TcMEPs in intraoperative neurophysiologic monitoring during spinal surgery. Conditioning stimulation techniques have been used for enhancement of transcranially evoked motor responses . Conditioning stimuli are applied prior to a test stimulus and increase the excitability of cortical and/or spinal motor neurons. According to Journe´e et al. , conditioning stimulation can be classified into two categories: (1) heteronymous stimulation in which conditioning stimuli are applied at a different site from a test stimulus,
J Clin Monit Comput
Fig. 2 The proportion of augmentation of motor evoked potentials by mt-TES recorded from the AH muscle at different repetitive rates (2, 5, and 10 Hz) compared to those elicited by single-train stimulation. Each individual train consists of five biphasic pulses 0.5-ms in duration (two phases of 0.25 ms in each pulse) and a 2.0-ms inter-
Fig. 3 Augmentation of motor evoked potentials recorded from the QF muscle by mt-TES at different repetitive rates (2, 5, and 10 Hz). Each individual train consists of five biphasic pulses 0.5-ms in duration (two phases of 0.25 ms in each pulse) and a 2.0-ms interpulse interval. The number of train stimuli was changed from two to seven. st-TES single-train transcranial electrical stimulation
and (2) homonymous stimulation in which both conditioning and test stimuli are applied at the same site. One homonymous conditioning stimulation technique is repetitive multipulse (train) TES, as described by Deletis , Deletis and Sala . He applied train TES repeatedly with an intertrain interval (ITI) of 0.5 or 1 s, and reported that each consecutive muscle response had increasing amplitude. In addition, MacDonald et al. [26,
pulse interval. The amplitude of potentials increased with the number of train stimuli. The strongest facilitation was observed at 5 Hz and the response amplitude increased up to 6.1 times on average. st-TES single-train transcranial electrical stimulation, mt-TES multi-train transcranial electrical stimulation
27] demonstrated progressive facilitation after the repetition of four pulse trains at 2–5 Hz during scoliosis surgery. Another homonymous conditioning is double-train TES (dt-TES) developed by Journe´e et al . They demonstrated that dt-TES elicited a marked facilitation of TcMEPs when the ITI was short (10 ms B ITI B 40 ms) or long (ITI C 0.1 s). Taking these previous conditioning techniques into account, train TES was delivered repeatedly at repetitive rates of 2, 5, and 10 Hz (ITI; 0.5, 0.2 and 0.1 s, respectively) in this study. The amplitudes of TcMEPs increased with the number of train stimuli in both the AH and QF, consistent with the finding of Deletis . The strongest augmentation of TcMEPs was observed at a repetition rate of 5 Hz (ITI; 0.2 s) in both muscles. The mechanism of augmentation of TcMEPs by mt-TES is unclear. However, central mechanisms at the level of the brain and spinal cord may be involved as previously reported in studies of conditioning stimulation techniques. Journe´e et al.  observed a cortical silent period after TES of about 0.1 s in anesthetized patients, which could be a possible explanation for the greater augmentation at 5 compared with 10 Hz. The disadvantage of homonymous facilitation using high intensity stimuli is the vigorous contractions and twitches of proximal muscle groups that interfere with surgery and put patients at risk of spinal cord injury, and spinal nerve root, eye, tongue, and lip injuries . However, accidental injury resulting from patient movement was not experienced in this study, and was avoided by brief surgical pauses (a few seconds) for monitoring of TcMEPs, coordinated between surgical and electrophysiological teams . In addition, no adverse events such as seizures, cardiac arrhythmias, and scalp burns, were observed in any of the patients.
J Clin Monit Comput
Fig. 4 The proportion of augmentation of motor evoked potentials by mt-TES recorded from the QF muscle at different repetitive rates (2, 5, and 10 Hz) compared to those elicited by single-train stimulation. Each individual train consists of five biphasic pulses 0.5-ms in duration (two phases of 0.25 ms in each pulse) and a 2.0-ms inter-
pulse interval. The amplitude of potentials increased with the number of train stimuli. The strongest facilitation was observed at 5 Hz and the response amplitude increased up to 8.0 times on average. st-TES single-train transcranial electrical stimulation, mt-TES multi-train transcranial electrical stimulation
To our knowledge, this is the first report to demonstrate an appropriate clinical setting for mt-TES systematically. However, there are a number of limitations to this study. First, train TES was applied up to 7 times because of the limitation of the equipment. More stimuli may result in greater augmentation of TcMEPs. Second, only patients without motor dysfunction were enrolled. Journe´e et al.  reported that facilitation with dt-TES appeared to be most effective when the TcMEPs elicited by st-TES were small or absent. TcMEPs are usually poor or absent in patients with preoperative neurological deficits. Third, only repetitive rates equal to or less than 10 Hz were assessed because of safety issues of repeated TES. As described above, the ITI of 10–40 ms (repetitive rate; 25–100 Hz) is optimal for augmentations of TcMEP responses when using dt-TES . However, continuous brain stimulation over a period of a few seconds with a frequency of 50–60 Hz was reported to easily induce seizures . Finally, there was no ‘‘true positive’’ case in which postoperative neurological deterioration was related to intraoperative critical changes of TcMEPs elicited by mt-TES. Thus, it is unclear how precisely TcMEPs elicited by mtTES can reflect intraoperative damage to the spinal cord and spinal nerve root compared with those elicited by stTES. Further clinical and basic investigation is required to assess the usefulness of mt-TES as a routine method in neurophysiologic monitoring during spinal surgery.
Ethical standards of Japan.
5 Conclusion Changing from conventional st-TES to mt-TES has potential to greatly enhance TcMEP responses.
Conflict of interest
The experiments comply with the current laws
References 1. Jellinek D, Jewkes D, Symon L. Noninvasive intraoperative monitoring of motor evoked potentials under propofol anesthesia: effect of spinal surgery on the amplitude and latency of motor evoked potentials. Neurosurgery. 1991;29:551–7. 2. Keller BP, Haghighi SS, Oro JJ, Eggerrs GWN. The effect of propofol anesthesia on transcortical electric evoked potentials in the rat. Neurosurgery. 1992;30:557–60. 3. Taylor BA, Fennelly ME, Taylor A, Farrell J. Temporal summation—the key to motor evoked potential spinal cord monitoring in humans. J Neurol Neurosurg Psychiat. 1993;56:104–6. 4. Jones SJ, Harrison R, Koh KF, Mendoza N, Crockard HA. Motor evoked potential monitoring during spinal surgery: response of distal limb muscle to transcranial cortical stimulation with pulse train. Electroencephalogr Clin Neurophysiol. 1996;100:375–83. 5. Pechstein U, Cedzich C, Nadstawek J, Schramm J. Transcranial high-frequency repetitive electrical stimulation for recording myogenic motor evoked potentials with the patient under general anesthesia. Neurosurgery. 1996;39:335–44. 6. Woodforth IJ, Hicks RG, Crawford MR, Stephen JP, Burke DJ. Variability of motor-evoked potentials recording during nitrous oxide anesthesia from the tibialis anterior muscle after transcranial electrical stimulation. Anesth Analg. 1996;82:744–9. 7. Tsutsui S, Yamada H, Hashizume H, Minamide A, Nakagawa Y, Iwasaki H, Yoshida M. Quantification of the proportion of motor neurons recruited by transcranial electrical stimulation during intraoperative motor evoked potential monitoring. J Clin Monit Comput. 2013;27:633–7. 8. Kothbauer K, Deletis V, Epstein FJ. Intraoperative spinal cord monitoring for intramedullary surgery: an essential adjunct. Pediatr Neurosurg. 1997;26:247–54. 9. Cioni B, Meglio M, Rossi GF. Intraoperative motor evoked potentials monitoring in spinal neurosurgery. Arch Ital Biol. 1999;137:115–26.
J Clin Monit Comput 10. Meylaerts SA, Jacobs MJ, van Iterson V, De Haan P, Kalkman CJ. Comparison of transcranial motor evoked potentials and somatosensory evoked potentials during thoracoabdominal aortic aneurysm repair. Ann Surg. 1999;230:742–9. 11. Kombos T, Suess O, Ciklatekerlio O, Brock M. Monitoring of intraoperative motor evoked potentials to increase the safety of surgery in and around the motor cortex. J Neurosurg. 2001;95:608–14. 12. Langeloo DD, Lelivelt A, Louis JH, Slappendel R, de Kleuver M. Transcranial electrical motor-evoked potential monitoring during surgery for spinal deformity: a study of 145 patients. Spine (Phila Pa 1976). 2003;28:1043–50. 13. Hilibrand AS, Schwartz DM, Sethuraman V, Vaccaro AR, Albert TJ. Comparison of transcranial electric motor and somatosensory evoked potential monitoring during cervical spine surgery. J Bone Jt Surg Am. 2004;86:1248–53. 14. Calancie B, Molano MR. Alarm criteria for motor-evoked potentials. What’s wrong with the ‘‘presence-or-absence’’ approach? Spine (Phila Pa 1976). 2008;33:406–14. 15. Sakaki K, Kawabata S, Ukegawa D, Hirai T, Ishii S, Tomori M, Inose H, Yoshii T, Tomizawa S, Kato T, Shinomiya K, Okawa A. Warning thresholds on the basis of origin of amplitude changes in transcranial electrical motor-evoked potential monitoring for cervical compression myelopathy. Spine (Phila Pa 1976). 2012;37:E913–21. 16. Muramoto A, Imagama S, Ito Z, Wakao N, Ando K, Tauchi R, Hirano K, Matsui H, Matsumoto T, Matsuyama Y, Ishigro N. The cutoff amplitude of transcranial motor-evoked potentials for predicting postoperative motor deficits in thoracic spine surgery. Spine (Phila Pa 1976). 2013;38:E21–7. 17. Iwasaki H, Tamaki T, Yoshida M, Ando M, Yamada H, Tsutsui S, Takami M. Efficacy and limitations of current methods of intraoperative spinal cord monitoring. J Orthop Sci. 2003;8:635–42. 18. Tsutsui S, Tamaki T, Yamada H, Iwasaki H, Takami M. Relationships between the changes in compound muscle action potentials and selective injuries to the spinal cord and spinal nerve roots. Clin Neurophysiol. 2003;114:1431–6. 19. MacDonald DB, Stigsby B, Al Homoud I, Abalkhail T, Mokeem A. Utility of motor evoked potentials for intraoperative nerve root monitoring. J Clin Neurophysiol. 2012;29:118–25. 20. Andersson G, Ohlin A. Spatial facilitation of motor evoked responses in monitoring during spinal surgery. Clin Neurophysiol. 1999;110:720–4. 21. Journe´e HL, Polak HE, de Kleuver M, Langeloo DD, Postma AA. Improved neuromonitoring during spinal surgery using doubletrain transcranial electrical stimulation. Med Biol Eng Comput. 2004;42:110–3. 22. Kakimoto M, Kawaguchi M, Yamamoto Y, Inoue S, Horiuchi T, Nakase H, Sakaki T, Furuya H. Tetanic stimulation of the peripheral nerve before transcranial electrical stimulation can
enlarge amplitudes of myogenic motor evoked potentials during general anesthesia with neuromuscular blockade. Anesthesiology. 2005;102:733–8. Frei FJ, Ryhult SE, Duitmann E, Hasler CC, Luetschg J, Erb TO. Intraoperative monitoring of motor evoked potentials in children undergoing spinal surgery. Spine (Phila Pa 1976). 2007;32:911–7. Hayashi H, Kawaguchi M, Yamamoto Y, Inoue S, Koizumi M, Ueda Y, Takakura Y, Furuya H. Evaluation of reliability of posttetanic motor evoked potential monitoring during spinal surgery under general anesthesia. Spine (Phila Pa 1976). 2008;33:E994–1000. Deletis V. Intraoperative neurophysiology and methodologies used to monitor the functional integrity of the motor system. In: Deletis V, Shils JL, editors. Neurophysiology in neurosurgery. New York: Academic Press; 2002. p. 25–51. MacDonald DB, Al Zayed Z, Khoudeir I, Stigsby B. Monitoring scoliosis surgery with combined multiple pulse transcranial electric motor and cortical somatosensory-evoked potentials from the lower and upper extremities. Spine (Phila Pa 1976). 2003;28:194–203. MacDonald DB, Al Zayed Z, Al SaddigiA. Four-limb muscle motor evoked potential and optimized somatosensory evoked potential monitoring with decussation assessment: results in 206 thoracolumbar spine surgeries. Eur Spine J. 2007;16(Suppl 2):171–87. Deletis V, Sala F. Corticospinal tract monitoring with D- and I-waves from the spinal cord and muscle MEPs from limb muscles. In: Nuwer MR, editor. Intraoperative monitoring of neural function. Handbook of clinical neurophysiology, vol. 8. Amsterdam: Elsevier; 2008. p. 235–51. MacDonald DB, Skinner S, Shils J, Yingling C. Intraoperative motor evoked potential monitoring—a position statement by the American Society of Neurophysiological Monitoring. Clin Neurophysiol. 2013;124:2291–316. Matsuda H, Shimazu A. Intraoperative spinal cord monitoring using electric responses to stimulation of caudal spinal cord or motor cortex. In: Desmedt JE, editor. Neuromonitoring in surgery. Amsterdam: Elsevier; 1989. p. 175–90. Journe´e HL, Polak HE, de Kleuver M. Conditioning stimulation techniques for enhancement of transcranially elicited evoked motor responses. Neurophysiol Clin. 2007;37:423–30. Hemmer LB, Zeeni C, Bebawy JF, Bendok BR, Cotton MA, Shah NB, Gupta DK, Koht A. The incidence of unacceptable movement with motor evoked potentials during craniotomy for aneurysm clipping. World Neurosurg. 2012;. doi:10.1016/j.wneu. 2012.05.034. Penfield W, Boldrey E. Somatic motor and sensory representation in the cerebral cortex of man as studied by electrical stimulation. Brain. 1937;60:339–443.