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A pitfall in magnetic stimulation for measuring central motor conduction time
Clinical Neurophysiology xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph
Editorial
A pitfall in magnetic stimulation for measuring central motor conduction time See Article, pages xxx–xxx
An interesting electrophysiological study of patients with Hirayama disease using magnetic stimulation is published in the current issue of Clinical Neurophysiology. Zheng et al. (2017) measured two types of central motor conduction time (CMCT) in patients with Hirayama disease: one is CMCT using the F-wave technique (CMCTF) and another is CMCT using magnetic motor root stimulation (CMCTM) (Rossini et al., 2015). The authors compared CMCTF and CMCTM, and they showed that CMCTM was abnormally prolonged compared with CMCTF. They interpreted this difference between the two types of CMCTs as indicating a prolongation of the motor root conduction time. Based on the difference between CMCTF and CMCTM, the motor root lesions must be located along the spinal nerves between the spinal motoneurons and the intervertebral foramina. In Hirayama disease, spinal motoneurons are involved through compression of the spinal cord by cervical vertebrae, which is induced by repeated or sustained neck flexion (Hirayama et al., 1987; Hirayama and Tokumaru, 2000). In particular, C8 or T1 spinal motoneurons are frequently involved. Thus, hand muscles are affected unilateral-dominantly, and the atrophic patterns of hand muscles in Hirayama disease are similar to those in ulnar neuropathy. Therefore, thenar muscles are relatively spared compared to hypothenar muscles, but all hand muscles can be involved to varying degrees. Zheng et al. (2017) proposed that lesions of the spinal motoneurons and motor roots may be present in some patients with Hirayama disease, based on the difference between CMCTF and CMCTM. Theoretically, the short segments of C8 or T1 spinal nerves could be involved in Hirayama disease by compression. However, a question arises: Can a neurophysiological study reliably detect a conduction delay of these very short segments? To detect the slight conduction delay precisely, highly-qualified neurophysiological examinations are required. In magnetic stimulation, there are several pitfalls to record motor evoked potentials (MEPs) from the atrophic muscles. MEPs in the upper extremities are usually recorded from intrinsic hand muscles such as the first dorsal interosseous (FDI), abductor digiti minimi (ADM), and abductor pollicis brevis (APB). Here, the biggest pitfall is the volume conduction from the non-targeted muscles to the target muscle. For measuring cortical latency, transcranial magnetic stimulation (TMS) should be performed during voluntary contraction of the target muscle (Rossini et al., 2015). Because voluntary contrac-
tion of the target muscle reduces the threshold for firing the spinal motoneurons innervating the target muscle, the target muscle is solely excited. Therefore, MEPs can be recorded from the target muscle almost exclusively; the volume conduction from the nontarget muscles to the target muscle is almost negligible, even in the recording from atrophic muscles. However, if TMS is performed during muscle relaxation, the non-target muscles are also excited (Ziemann et al., 2004). Therefore, MEPs are strongly affected by volume conduction from the non-target muscles to the target muscle, particularly in the recording from atrophic APB (Matsumoto et al., 2010). Thus, the recording during muscle relaxation is an inappropriate method to measure the precise latency reflecting the motor pathway from cortical motoneurons to the target muscle. To measure root latency, magnetic motor root stimulation should be performed during muscle relaxation. Here, the target muscle should be the ADM or FDI, but not the APB (Matsumoto et al., 2010). Magnetic motor root stimulation over the C8 or T1 spinous process generates an impulse at the level of the intervertebral foramina (Ugawa et al., 1989). The impulse travels down toward the hand muscles through the motor roots, brachial plexus, and peripheral nerves (i.e., the impulse travels through both the median and ulnar nerves). Thus, all the intrinsic hand muscles such as the FDI, ADM, and APB are excited. In recordings from the APB, volume conduction is not negligible: MEPs are affected by the volume conduction from non-target muscles that are innervated by the ulnar nerve, e.g. the interosseous and lumbrical muscles, particularly, in the recording from an atrophic APB. However, in the recording from the ADM or FDI, the volume conduction is usually negligible: MEPs are difficult to affect by the volume conduction from the non-target muscles that are innervated by the median nerve due to the anatomical distance. However, in recordings from an atrophic ADM or FDI, volume conduction may not be negligible. To measure the root latency reflecting the motor pathway from the motor roots to the atrophic target muscle precisely, the collision technique is required (Kimura, 1976; Matsumoto et al., 2010). For example, in the recording from an atrophic FDI, magnetic motor root stimulation and supramaximal electrical stimulation of the median nerve at the wrist should be performed simultaneously. Orthodromic impulses generated by magnetic motor root stimulation collide with antidromic impulses generated by median nerve stimulation. Therefore, the orthodromic impulses cannot reach any of the hand muscles innervated by median nerve such
http://dx.doi.org/10.1016/j.clinph.2017.08.002 1388-2457/Ó 2017 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
2
Editorial / Clinical Neurophysiology xxx (2017) xxx–xxx
as the APB and opponens pollicis, but reach the atrophic FDI. As a result, the precise latency reflecting the motor pathway from the motor roots to the atrophic FDI is obtainable. Thus, in the collision technique, supramaximal electrical stimulation at the wrist should be applied to the ‘peripheral nerve of no interest’, i.e., in the case of ADM and FDI the median nerve, and in the case of the APB the ulnar nerve. Using this technique, all three atrophic muscles (i.e. the FDI, ADM, and APB) can be targeted in magnetic motor root stimulation. When measuring CMCT, this pitfall must always be considered. However, to measure cortical latency or root latency precisely in patients who have muscular weakness and atrophy, magnetic stimulation becomes technically demanding. In Hirayama disease, the patients frequently could have difficulty maintaining voluntary contraction. In this case, TMS may only be applied during muscle relaxation. In addition, magnetic motor root stimulation using the collision technique is not routinely recommended because it is a complicated procedure. Zheng et al. (2017) performed TMS during muscle relaxation and magnetic motor root stimulation without using the collision technique in 41 patients with Hirayama disease. Therefore, it would be valuable to use another approach to verify their contention that motor root lesions may be present in Hirayama disease. Here, we recommend planning a study on peripheral motor conduction time (PMCT) calculated using the F-wave technique (PMCTF) and calculated by motor root stimulation using the collision technique (PMCTM). The motor root conduction time calculated using the difference between CMCTF and CMCTM is an indirect method to detect motor root lesions, whereas the motor root conduction time calculated using the difference between PMCTF and PMCTM is a direct method. Currently, there are three methods of motor root stimulation (Matsumoto et al., 2013): electrical stimulation using a high-voltage electrical stimulator (Rossini et al., 1985; Ugawa et al., 1989), electrical stimulation using needle electrodes (Vucic et al., 2006) and magnetic stimulation (Ugawa et al., 1989; Matsumoto et al., 2010, 2013). Any type of stimulation using the collision technique could provide more precise results. This pitfall should be kept in mind for the interpretation of CMCT measurements also in other studies. For example, Matamala et al. (2017) also applied TMS to patients with Hirayama disease to study motor cortical excitability. They showed normal intracortical inhibition in Hirayama disease using the threshold tracking technique and proposed that this could distinguish Hirayama disease from early-onset amyotrophic lateral sclerosis where inhibition is decreased. In these two interesting recent papers on the pathophysiology of Hirayama disease (Matamala et al., 2017; Zheng et al., 2017), TMS was performed during muscle relaxation, and MEPs were recorded from the APB, implying the risk that the MEP results may have been affected by volume conduction. Therefore, as described by Matamala et al. (2017), these MEP data should be interpreted with caution. Volume conduction
from neighboring hand muscles needs to be excluded or quantified, in order to obtain accurate pathophysiological insight. In summary, in patients who have atrophic hand paresis, such as in Hirayama disease, magnetic stimulation is technically demanding. The volume conduction pitfall should be kept in mind to determine the pathophysiology of such diseases correctly. Conflict of interest None. References Hirayama K, Tomonaga M, Kitano K, Yamada T, Kojima S, Arai K. Focal cervical poliopathy causing juvenile muscular atrophy of distal upper extremity: a pathological study. J Neurol Neurosurg Psych 1987;50:285–90. Hirayama K, Tokumaru Y. Cervical dural sac and spinal cord in juvenile muscular atrophy of distal upper extremity. Neurology 2000;54:1922–6. Kimura J. Collision technique. Physiologic block of nerve impulses in studies of motor nerve conduction velocity. Neurology 1976;26:680–2. Matamala JM, Geevasinga N, Huynh W, Dharmadasa T, Howells J, Simon NG, et al. Cortical function and corticomotoneuronal adaptation in monomelic amyotrophy. Clin Neurophysiol 2017;128:1488–95. Matsumoto L, Hanajima R, Matsumoto H, Ohminami S, Terao Y, Tsuji S, et al. Supramaximal responses can be elicited in hand muscles by magnetic stimulation of the cervical motor roots. Brain Stimul 2010;3:153–60. Matsumoto H, Hanajima R, Terao Y, Ugawa Y. Magnetic-motor-root stimulation: review. Clin Neurophysiol 2013;124:1055–67. Rossini PM, Di Stefano E, Stanzione P. Nerve impulse propagation along central and peripheral fast conducting motor and sensory pathways in man. Electroencephalogr Clin Neurophysiol 1985;60:320–34. Rossini PM, Burke D, Chen R, Cohen LG, Daskalakis Z, Di Iorio R, et al. Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee. Clin Neurophysiol 2015;126:1071–107. Ugawa Y, Rothwell JC, Day BL, Thompson PD, Marsden CD. Magnetic stimulation over the spinal enlargements. J Neurol Neurosurg Psych 1989;52:1025–32. Vucic S, Cairns KD, Black KR, Chong PS, Cros D. Cervical nerve root stimulation. Part I: technical aspects and normal data. Clin Neurophysiol 2006;117:392–7. Zheng C, Zhu D, Lu F, Zhu Y, Ma X, Xia X, et al. A double determination of central motor conduction time in the assessment of Hirayama disease. Clin Neurophysiol 2017 [this issue]. Ziemann U, Ilic´ TV, Alle H, Meintzschel F. Cortico-motoneuronal excitation of three hand muscles determined by a novel penta-stimulation technique. Brain 2004;127:1887–98.
⇑
Hideyuki Matsumoto Department of Neurology, Japanese Red Cross Medical Center, 4-1-22 Hiroo, Shibuya-ku, Tokyo 150-8935, Japan ⇑ Corresponding author. Fax: +81 3 3409 1604. E-mail address: [email protected] Yoshikazu Ugawa 1 Department of Neurology, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan E-mail addresses: [email protected]
1
Fax: +81 24 548 3797.
Contents lists available at ScienceDirect
Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph
Editorial
A pitfall in magnetic stimulation for measuring central motor conduction time See Article, pages xxx–xxx
An interesting electrophysiological study of patients with Hirayama disease using magnetic stimulation is published in the current issue of Clinical Neurophysiology. Zheng et al. (2017) measured two types of central motor conduction time (CMCT) in patients with Hirayama disease: one is CMCT using the F-wave technique (CMCTF) and another is CMCT using magnetic motor root stimulation (CMCTM) (Rossini et al., 2015). The authors compared CMCTF and CMCTM, and they showed that CMCTM was abnormally prolonged compared with CMCTF. They interpreted this difference between the two types of CMCTs as indicating a prolongation of the motor root conduction time. Based on the difference between CMCTF and CMCTM, the motor root lesions must be located along the spinal nerves between the spinal motoneurons and the intervertebral foramina. In Hirayama disease, spinal motoneurons are involved through compression of the spinal cord by cervical vertebrae, which is induced by repeated or sustained neck flexion (Hirayama et al., 1987; Hirayama and Tokumaru, 2000). In particular, C8 or T1 spinal motoneurons are frequently involved. Thus, hand muscles are affected unilateral-dominantly, and the atrophic patterns of hand muscles in Hirayama disease are similar to those in ulnar neuropathy. Therefore, thenar muscles are relatively spared compared to hypothenar muscles, but all hand muscles can be involved to varying degrees. Zheng et al. (2017) proposed that lesions of the spinal motoneurons and motor roots may be present in some patients with Hirayama disease, based on the difference between CMCTF and CMCTM. Theoretically, the short segments of C8 or T1 spinal nerves could be involved in Hirayama disease by compression. However, a question arises: Can a neurophysiological study reliably detect a conduction delay of these very short segments? To detect the slight conduction delay precisely, highly-qualified neurophysiological examinations are required. In magnetic stimulation, there are several pitfalls to record motor evoked potentials (MEPs) from the atrophic muscles. MEPs in the upper extremities are usually recorded from intrinsic hand muscles such as the first dorsal interosseous (FDI), abductor digiti minimi (ADM), and abductor pollicis brevis (APB). Here, the biggest pitfall is the volume conduction from the non-targeted muscles to the target muscle. For measuring cortical latency, transcranial magnetic stimulation (TMS) should be performed during voluntary contraction of the target muscle (Rossini et al., 2015). Because voluntary contrac-
tion of the target muscle reduces the threshold for firing the spinal motoneurons innervating the target muscle, the target muscle is solely excited. Therefore, MEPs can be recorded from the target muscle almost exclusively; the volume conduction from the nontarget muscles to the target muscle is almost negligible, even in the recording from atrophic muscles. However, if TMS is performed during muscle relaxation, the non-target muscles are also excited (Ziemann et al., 2004). Therefore, MEPs are strongly affected by volume conduction from the non-target muscles to the target muscle, particularly in the recording from atrophic APB (Matsumoto et al., 2010). Thus, the recording during muscle relaxation is an inappropriate method to measure the precise latency reflecting the motor pathway from cortical motoneurons to the target muscle. To measure root latency, magnetic motor root stimulation should be performed during muscle relaxation. Here, the target muscle should be the ADM or FDI, but not the APB (Matsumoto et al., 2010). Magnetic motor root stimulation over the C8 or T1 spinous process generates an impulse at the level of the intervertebral foramina (Ugawa et al., 1989). The impulse travels down toward the hand muscles through the motor roots, brachial plexus, and peripheral nerves (i.e., the impulse travels through both the median and ulnar nerves). Thus, all the intrinsic hand muscles such as the FDI, ADM, and APB are excited. In recordings from the APB, volume conduction is not negligible: MEPs are affected by the volume conduction from non-target muscles that are innervated by the ulnar nerve, e.g. the interosseous and lumbrical muscles, particularly, in the recording from an atrophic APB. However, in the recording from the ADM or FDI, the volume conduction is usually negligible: MEPs are difficult to affect by the volume conduction from the non-target muscles that are innervated by the median nerve due to the anatomical distance. However, in recordings from an atrophic ADM or FDI, volume conduction may not be negligible. To measure the root latency reflecting the motor pathway from the motor roots to the atrophic target muscle precisely, the collision technique is required (Kimura, 1976; Matsumoto et al., 2010). For example, in the recording from an atrophic FDI, magnetic motor root stimulation and supramaximal electrical stimulation of the median nerve at the wrist should be performed simultaneously. Orthodromic impulses generated by magnetic motor root stimulation collide with antidromic impulses generated by median nerve stimulation. Therefore, the orthodromic impulses cannot reach any of the hand muscles innervated by median nerve such
http://dx.doi.org/10.1016/j.clinph.2017.08.002 1388-2457/Ó 2017 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
2
Editorial / Clinical Neurophysiology xxx (2017) xxx–xxx
as the APB and opponens pollicis, but reach the atrophic FDI. As a result, the precise latency reflecting the motor pathway from the motor roots to the atrophic FDI is obtainable. Thus, in the collision technique, supramaximal electrical stimulation at the wrist should be applied to the ‘peripheral nerve of no interest’, i.e., in the case of ADM and FDI the median nerve, and in the case of the APB the ulnar nerve. Using this technique, all three atrophic muscles (i.e. the FDI, ADM, and APB) can be targeted in magnetic motor root stimulation. When measuring CMCT, this pitfall must always be considered. However, to measure cortical latency or root latency precisely in patients who have muscular weakness and atrophy, magnetic stimulation becomes technically demanding. In Hirayama disease, the patients frequently could have difficulty maintaining voluntary contraction. In this case, TMS may only be applied during muscle relaxation. In addition, magnetic motor root stimulation using the collision technique is not routinely recommended because it is a complicated procedure. Zheng et al. (2017) performed TMS during muscle relaxation and magnetic motor root stimulation without using the collision technique in 41 patients with Hirayama disease. Therefore, it would be valuable to use another approach to verify their contention that motor root lesions may be present in Hirayama disease. Here, we recommend planning a study on peripheral motor conduction time (PMCT) calculated using the F-wave technique (PMCTF) and calculated by motor root stimulation using the collision technique (PMCTM). The motor root conduction time calculated using the difference between CMCTF and CMCTM is an indirect method to detect motor root lesions, whereas the motor root conduction time calculated using the difference between PMCTF and PMCTM is a direct method. Currently, there are three methods of motor root stimulation (Matsumoto et al., 2013): electrical stimulation using a high-voltage electrical stimulator (Rossini et al., 1985; Ugawa et al., 1989), electrical stimulation using needle electrodes (Vucic et al., 2006) and magnetic stimulation (Ugawa et al., 1989; Matsumoto et al., 2010, 2013). Any type of stimulation using the collision technique could provide more precise results. This pitfall should be kept in mind for the interpretation of CMCT measurements also in other studies. For example, Matamala et al. (2017) also applied TMS to patients with Hirayama disease to study motor cortical excitability. They showed normal intracortical inhibition in Hirayama disease using the threshold tracking technique and proposed that this could distinguish Hirayama disease from early-onset amyotrophic lateral sclerosis where inhibition is decreased. In these two interesting recent papers on the pathophysiology of Hirayama disease (Matamala et al., 2017; Zheng et al., 2017), TMS was performed during muscle relaxation, and MEPs were recorded from the APB, implying the risk that the MEP results may have been affected by volume conduction. Therefore, as described by Matamala et al. (2017), these MEP data should be interpreted with caution. Volume conduction
from neighboring hand muscles needs to be excluded or quantified, in order to obtain accurate pathophysiological insight. In summary, in patients who have atrophic hand paresis, such as in Hirayama disease, magnetic stimulation is technically demanding. The volume conduction pitfall should be kept in mind to determine the pathophysiology of such diseases correctly. Conflict of interest None. References Hirayama K, Tomonaga M, Kitano K, Yamada T, Kojima S, Arai K. Focal cervical poliopathy causing juvenile muscular atrophy of distal upper extremity: a pathological study. J Neurol Neurosurg Psych 1987;50:285–90. Hirayama K, Tokumaru Y. Cervical dural sac and spinal cord in juvenile muscular atrophy of distal upper extremity. Neurology 2000;54:1922–6. Kimura J. Collision technique. Physiologic block of nerve impulses in studies of motor nerve conduction velocity. Neurology 1976;26:680–2. Matamala JM, Geevasinga N, Huynh W, Dharmadasa T, Howells J, Simon NG, et al. Cortical function and corticomotoneuronal adaptation in monomelic amyotrophy. Clin Neurophysiol 2017;128:1488–95. Matsumoto L, Hanajima R, Matsumoto H, Ohminami S, Terao Y, Tsuji S, et al. Supramaximal responses can be elicited in hand muscles by magnetic stimulation of the cervical motor roots. Brain Stimul 2010;3:153–60. Matsumoto H, Hanajima R, Terao Y, Ugawa Y. Magnetic-motor-root stimulation: review. Clin Neurophysiol 2013;124:1055–67. Rossini PM, Di Stefano E, Stanzione P. Nerve impulse propagation along central and peripheral fast conducting motor and sensory pathways in man. Electroencephalogr Clin Neurophysiol 1985;60:320–34. Rossini PM, Burke D, Chen R, Cohen LG, Daskalakis Z, Di Iorio R, et al. Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee. Clin Neurophysiol 2015;126:1071–107. Ugawa Y, Rothwell JC, Day BL, Thompson PD, Marsden CD. Magnetic stimulation over the spinal enlargements. J Neurol Neurosurg Psych 1989;52:1025–32. Vucic S, Cairns KD, Black KR, Chong PS, Cros D. Cervical nerve root stimulation. Part I: technical aspects and normal data. Clin Neurophysiol 2006;117:392–7. Zheng C, Zhu D, Lu F, Zhu Y, Ma X, Xia X, et al. A double determination of central motor conduction time in the assessment of Hirayama disease. Clin Neurophysiol 2017 [this issue]. Ziemann U, Ilic´ TV, Alle H, Meintzschel F. Cortico-motoneuronal excitation of three hand muscles determined by a novel penta-stimulation technique. Brain 2004;127:1887–98.
⇑
Hideyuki Matsumoto Department of Neurology, Japanese Red Cross Medical Center, 4-1-22 Hiroo, Shibuya-ku, Tokyo 150-8935, Japan ⇑ Corresponding author. Fax: +81 3 3409 1604. E-mail address: [email protected] Yoshikazu Ugawa 1 Department of Neurology, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan E-mail addresses: [email protected]
1
Fax: +81 24 548 3797.