1351 CLINICAL NOTE Ipsilateral Motor Pathway Confirmed by Combined Brain Mapping of a Patient With Hemiparetic Stroke: A Case Report Yun-Hee Kim, MD, Sung Ho Jang, MD, Woo Mok Byun, MD, Bong Soo Han, PhD, Kang-Hee Lee, MD, Sang Ho Ahn, MD ABSTRACT. Kim Y-H, Jang SH, Byun WM, Han BS, Lee K-H, Ahn SH. Ipsilateral motor pathway confirmed by combined brain mapping of a patient with hemiparetic stroke: a case report. Arch Phys Med Rehabil 2004;85:1351-3. This study investigated the motor control pathway using both functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) in a patient with left hemiparesis with an infarction on the posterior limb of the right internal capsule. fMRI was performed using the blood oxygen level– dependent technique at 1.5T with a standard head coil. The motor activation task consisted of hand grasp-release movements in 1-Hz cycles. TMS was performed using a butterfly coil; the intersection of the wings (center of the coil) was applied tangentially to the scalp 1.0cm apart. Stimulation was performed at 100% of maximal output. Motor evoked potentials (MEPs) from both abductor pollicis brevis (APB) muscles were obtained simultaneously. fMRI showed that the unaffected (left) primary sensorimotor cortex (SM1) was activated by movements of the unaffected (right) hand. Conversely, the bilateral SM1 were activated by movements of the affected (left) hand. Brain mapping using TMS showed that ipsilateral MEPs were obtained at the affected (left) APB muscle when the unaffected (left) motor cortex was stimulated. We concluded that the ipsilateral motor pathway from the unaffected motor cortex to the affected hand was present in this patient. Key Words: Brain mapping; Case report; Hemiplegia; Magnetic resonance imaging; Motor skills; Rehabilitation; Stroke. © 2004 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation T IS VERY IMPORTANT to understand the motor recovery mechanisms in stroke patients. However, in the current litIerature, these mechanisms have not been clearly elucidated. Cramer et al1 reported that the poststroke motor recovery mechanisms consist of a reorganization into areas adjacent to the injured primary motor cortex (M1), the unmasking of the From the Department of Physical Medicine & Rehabilitation, School of Medicine Sungkyunkwan University, Samsung Medical Center (Kim); Departments of Physical Medicine & Rehabilitation (Jang, Lee, Ahn) and Diagnostic Radiology (Byun), Yeungnam University College of Medicine; and Department of Radiology, Kyungpook National University School of Medicine (Han), Taegu, South Korea. Supported by the Korean Brain Neuroinformatics Research Program, Korean Ministry of Science and Technology. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the author(s) or on any organization with which the author(s) is/are associated. Reprint requests to Sung Ho Jang, MD, Dept of Physical Medicine & Rehabilitation, School of Medicine, Yeungnam University, 317-1, Daemyungdong, Namku, Taegu 705-717, South Korea, e-mail: strokerehab@hanmail.net. 0003-9993/04/8508-8502$30.00/0 doi:10.1016/j.apmr.2003.08.102 ipsilateral motor pathway from the unaffected motor cortex to the affected hand, and the activation of the supplementary motor area. Of these mechanisms, the ipsilateral motor pathway is the most actively researched and has been reported in several diseases.2-6 Brain mapping is an indispensable tool for investigating the recovery mechanisms of an injured brain. Mapping using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS is an ideal combination of noninvasive brain mapping methods) for studying motor function,7 because fMRI has excellent spatial resolution and TMS can identity the characteristics of motor pathway. The fact that the unaffected hemisphere can contribute to the motor recovery after stroke has been shown using transcranial Doppler ultrasonography,8 positron emission tomography,4 fMRI,1,5 and TMS.5,9,10 However, no study has mapped this motor pathway with a combined brain mapping technique using fMRI and TMS. We report on a patient with hemiparetic stroke who showed an ipsilateral motor pathway from the unaffected motor cortex to the affected hand, as evaluated by fMRI and TMS. CASE DESCRIPTION A right-handed man in his early forties with left hemiparesis was referred to our hospital for evaluation of motor function and rehabilitation. Focal high-signal intensity in the posterior limb of the right internal capsule was seen on a fluid-attenuated inversion recovery (FLAIR) image of brain magnetic resonance imaging (fig 1A). His left upper and lower extremities were completely paralyzed initially but recovered slowly over 3 months. At the time of evaluation (6mo after onset), he was able to grasp and release an object and walk with spastic gait pattern. However, he could not carry out fine motor activity with his left hand. Sustained mirror movements of the unaffected (right) hand were triggered by movements of the unaffected (left) hand, but there was no mirror movement on the left hand triggered by movements of the affected (right) hand. Functional Magnetic Resonance Imaging The blood oxygenation level– dependent (BOLD) fMRI measurement, which uses the echo planar imaging (EPI) technique, was performed using a 1.5-T magnetic resonance scannera with a standard head coil. For the anatomically based images, 13 axial 5-mm–thick T1-weighted conventional spin echo images were obtained using a matrix size of 128⫻128mm and a field of view (FOV) of 210mm, parallel to the bicommissure line of Talairach (anterior commissure–posterior commissure line). The EPI BOLD images were acquired over the same 13 axial sections for each epoch, producing a total of 780 images for each subject. Imaging parameters of each experiment consisted of time to repetition and time to echo in spin equal to 2 seconds and 6ms, respectively, with an FOV of 210mm, a matrix size of 64⫻64mm, and a slice thickness of 5mm. For the motor task paradigm, hand grasp-release moveArch Phys Med Rehabil Vol 85, August 2004 1352 IPSILATERAL MOTOR PATHWAY IN HEMIPARETIC STROKE, Kim (left) hemisphere. The latency and amplitude of contralateral and ipsilateral MEPs from the 3 sites were 21.2ms and 1482␮V and 27.5ms and 132␮V, respectively, at (– 6, 0); 23.3ms and 1118␮V and 25.1ms and 272␮V, respectively, at (–7, 0); and 22.2ms and 1121␮V and 29.1ms and 154␮V, respectively, at (– 6, 1) (see also figs 2B, 2C). Fig 1. (A) Focal high-signal intensity in the posterior limb of the right internal capsule, seen on FLAIR image. (B) fMRI shows activation of the left primary sensorimotor cortex (SM1) by the unaffected (right) hand movements. (C) By comparison, activation of bilateral SM1 was seen by the affected (left) hand movements. ments were performed at 1 Hz in a 15 seconds on–15 seconds off cycle. The differences in magnetic resonance signals between the rest and stimulus periods were then analyzed with Stimulate,b a software used for fMRI data analysis.11 Statistical maps indicating patterns of activation were generated using the Student t test. The pixels with P values less than .001 were chosen to be activated. In addition, the area in which 4 or more pixels were simultaneously activated was finally selected using cluster analysis. Regions of interest were drawn around the primary sensorimotor cortex (SM1), premotor cortex, and supplementary motor area by a neuroradiologist. The SM1 extends from the precentral to the postcentral gyrus. The premotor cortex extends from precentral sulcus to a rostral limit halfway between central culcus and the anterior-most extent of the brain, brain vertex to Sylvian fissure, and lateral brain surface to supplementary motor area. The supplementary motor area extends rostrocaudally, as is the case with the premotor cortex, from the brain vertex to the cingulate sulcus and from the midline to the white matter underlying the mesial cortex. fMRI showed that the unaffected (left) SM1 was activated by movements of the unaffected (right) hand (fig 1B). Additionally, the bilateral SM1 was activated by movements of the affected (left) hand (fig 1C). Transcranial Magnetic Stimulation TMS was performed using a Dantec Mag2 stimulatorc and a 55-mm (mean diameter) butterfly coil. A cloth, marked with spacings 1cm apart and with Cz referenced to the intersection of midsagittal and interaural lines, was placed on the scalp. The intersection of the wings (center of the coil) was applied tangentially to the scalp, and the handgrips were placed so that they were parallel to the midsagittal line and faced the back. Magnetic stimulation was applied at 100% of maximal output. Motor evoked potentials (MEPs) were obtained from both abductor pollicis brevis (APB) muscles in the relaxed state. Each site was stimulated 3 times at 1-cm intervals, from which the shortest latency and the average of the peak-to-peak amplitudes were determined. The site where the excitatory threshold was the lowest, latency the shortest, and average amplitude the largest was determined as the optimal scalp site. The MEP (latency, 26.5ms; amplitude, 130␮V) of the affected (left) APB muscle was evoked from 1 site (6, 0) in the affected (right) hemisphere (fig 2A). The optimal scalp site was (– 6, 0) in the unaffected (left) hemisphere for the unaffected right APB, and the excitatory threshold was 80%. The contralateral MEPs from the unaffected (right) APB in the unaffected (left) hemisphere were obtained from 6 sites around the optimal scalp site (– 6, 0) and the ipsilateral MEPs from the affected (left) APB were obtained from 3 sites in the unaffected Arch Phys Med Rehabil Vol 85, August 2004 DISCUSSION Among many noninvasive brain mapping techniques, TMS and fMRI have several advantages over other methods in evaluation of motor functions, because they can be used repeatedly and they produce no ionizing radiation. Furthermore, TMS and fMRI allow for very accurate brain mapping of motor function when they are used at the same time.7 That is, fMRI can localize the activation site precisely because of its excellent spatial resolution. However, because fMRI often shows the ipsilateral motor cortex activation in a normal subject, alone it cannot determine whether the ipsilateral motor pathway found in a patient with brain injury previously existed or resulted from motor recovery.12 TMS, however, is useful in confirming the ipsilateral MEP as a motor recovery mechanism because ipsilateral MEPs cannot be evoked in a relaxed hand muscle of an able-bodied person.2,13 The disadvantage of TMS is its poor spatial resolution. In this report, we showed the presence of the Fig 2. (A) Diagram of motor pathway evoked by TMS. MEPs to the affected (left) APB muscle were evoked from only 1 site (6, 0) of the affected (right) motor cortex. MEPs to the unaffected (right) APB muscle were evoked from 6 sites of the unaffected (left) motor cortex and the optimal scalp position (– 6, 0). Ipsilateral motor pathway from the unaffected (left) motor cortex to the affected (left) APB muscle was present (dotted line). (B) Contralateral MEPs showed higher amplitude and shorter latency compared with (C) those of ipsilateral MEPs. IPSILATERAL MOTOR PATHWAY IN HEMIPARETIC STROKE, Kim ipsilateral motor pathway from the unaffected motor cortex to the affected hand in a patient with hemiparetic stroke using combined brain mapping technique of fMRI and TMS. The ipsilateral motor pathway observed after brain injury can be grossly classified into the corticospinal tract or the noncorticospinal tract, which will differ depending on the time of brain injury.2,14 According to Muller et al,14 the ipsilateral corticospinal tract exists at birth, becomes inhibited gradually as the brain matures (around the age of 10) and so ipsilateral MEPs cannot be evoked. Motor recovery after a brain injury in an immature brain involves the corticospinal tract; in the mature, recovery involves the noncorticospinal pathways, most likely the corticoreticulospinal tract.2,14 Other pathways, such as collateral sprouting or transcallosal pathway, have been considered as well.6,14 TMS can distinguish between the motor pathway through the corticospinal tract and the noncorticospinal tract by analyzing the characteristics of the MEPs.15 The ipsilateral motor pathway that originates from the corticospinal tract has a latency and amplitude of the ipsilateral MEP, which is very similar to that of a contralateral MEP.2,5 By comparison, an ipsilateral MEP, which originates from the noncorticospinal tract, has a delayed latency and smaller amplitude compared with that of the contralateral MEP.2,6,14 Previous studies9,10 have shown that ipsilateral MEPs observed in patients with hemiparetic stroke are usually small, with latencies of 5 to 14ms longer than those of the contralateral MEPs. In our study, ipsilateral MEPs showed delayed latency and smaller amplitudes than those of the contralateral MEPs (latency, 5.3ms; delayed amplitude, 10% greater than at the hot spot of the left motor cortex). Therefore, the ipsilateral motor pathway observed in this case seemed to be attributable to the noncorticospinal tract. The ipsilateral motor pathway is an important recovery mechanism in terms of stroke rehabilitation. The ipsilateral (unaffected) motor cortex seems to play a significant role in recovery in the early stage after stroke and its role changes with time.16-18 Recent studies17,18 have shown that an increase in the affected (contralateral) and a decrease in the unaffected (ipsilateral) motor cortex activity occur with motor recovery in stroke patients. Therefore, inhibition of ipsilateral (unaffected) motor cortex activity and facilitation of contralateral (affected) motor cortex activity can be an important strategy for improved motor recovery hemiparetic stroke in patients. In previous studies12,19,20 with healthy subjects, the ipsilateral motor cortex has been activated by various exercise conditions, such as force, complexity, or handedness. We believe that the ipsilateral motor pathway can be manipulated in therapy if the relationship between the ipsilateral motor pathway and various exercise conditions in stroke patients is clarified further. 1353 CONCLUSIONS The ipsilateral motor pathway from the unaffected motor cortex to the affected hand was shown by the combined brain mapping with fMRI and TMS. The clinical significance and characteristics of the ipsilateral motor pathway should be elucidated with further study. hemispheric lesions demonstrated by magnetic brain stimulation. Exp Brain Res 1991;83:419-26. 3. Caramia MD, Telera S, Palmieri MG, et al. Ipsilateral motor activation in patients with cerebral glioma. Neurology 1998;51: 196-202. 4. Chollet F, DiPiero V, Wise RJ, Brooks DJ, Dolan RJ, Frackowiak RS. The functional anatomy of motor recovery after stroke in humans: a study with positron emission tomography. Ann Neurol 1991;9:63-71. 5. Jang SH, Byun WM, Chang Y, Han BS, Ahn SH. Combined functional magnetic resonance imaging and transcranial magnetic stimulation evidence of ipsilateral motor pathway with congenital brain disorder: a case report. Arch Phys Med Rehabil 2001;82: 1733-6. 6. Maegaki Y, Maeoka Y, Ishii S, et al. Mechanisms of central motor reorganization in pediatric hemiplegic patients. Neuropediatrics 1997;28:168-74. 7. Macdonell RA, Jackson GD, Curatolo JM, et al. Motor cortex localization using functional MRI and transcranial magnetic stimulation. Neurology 1999;53:1462-7. 8. Silvestrini M, Troisi E, Matteis M, Cupini LM, Caltagirone C. Involvement of the healthy hemisphere in recovery from aphasia and motor deficit in patients with cortical ischemic infarction: a transcranial Doppler study. Neurology 1995;45:1815-20. 9. Netz J, Lammers T, Homberg V. Reorganization of motor output in the non-affected hemisphere after stroke. Brain 1997;120:157986. 10. Turton A, Wroe S, Trepte N, Fraser C, Lemon RN. Contralateral and ipsilateral EMG responses to transcranial magnetic stimulation during recovery of arm and hand function after stroke. Electroencephalogr Clin Neurophysiol 1996;101:316-28. 11. Strupp JP. Stimulate: a GUI based fMRI analysis software package [abstract]. Neuroimage 1996;3:S607. 12. Kim SG, Ashe J, Hendrich K, et al. Functional magnetic resonance imaging of motor cortex: hemispheric asymmetry and handedness. Science 1993;261:615-7. 13. Wassermann EM, Fuhr P, Cohen LG, Hallet M. Effects of transcranial magnetic stimulation on ipsilateral muscles. Neurology 1991;41:1795-9. 14. Muller K, Kass-Iliyya F, Reitz M. Ontogeny of ipsilateral corticospinal projections: a developmental study with transcranial magnetic stimulation. Ann Neurol 1997;42:705-11. 15. Rossini PM, Tecchio F, Pizzella V, et al. On the reorganization of sensory hand areas after mono-hemispheric lesion: a functional (MEG)/anatomical (MRI) integrative study. Brain Res 1998;782: 153-66. 16. Liepert J, Hamzei F, Weiller C. Motor cortex disinhibition of the unaffected hemisphere after acute stroke. Muscle Nerve 2000;23: 1761-3. 17. Marshall RS, Perera GM, Lazar RM, Krakauer JW, Constantine RC, DeLaPaz RL. Evolution of cortical activation during recovery from corticospinal tract infarction. Stroke 2000;31:656-61. 18. Jang SH, Kim YH, Cho SH, Chang Y, Lee ZI, Lee JS. Cortical reorganization associated with motor recovery in hemiparetic stroke patients. Neuroreport 2003;14:1305-10. 19. Cramer SC, Weisskoff RM, Schaechter JD, et al. Motor cortex activation is related to force of squeezing. Hum Brain Mapp 2002;16:197-205. 20. Shibasaki H, Sadato N, Lyshkow H, et al. Both primary motor cortex and supplementary motor area play an important role in complex finger movement. Brain 1993;116(Pt 6):1387-98. References 1. Cramer SC, Nelles G, Benson RR, et al. A functional MRI study of subjects recovered from hemiparetic stroke. Stroke 1997;28: 2518-27. 2. Benecke R, Meyer BU, Freund HJ. Reorganization of descending motor pathways in patients after hemispherectomy and severe Suppliers a. Vision; Siemens, Wittelsbacherplatz 2, 80333 München, Germany. b. Center for Magnetic Resonance Research, University of Minnesota Medical School, 2021 Sixth St SE, Minneapolis, MN 55455. c. Medtronic-Dantec, Tonsbakken 16-18, DK-2740 Skovlunde, Denmark. Arch Phys Med Rehabil Vol 85, August 2004