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Remote effect of repetitive transcranial magnetic stimulation on the cerebellum of spinocerebellar degeneration patients
International Congress Series 1270 (2004) 233 – 236
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Remote effect of repetitive transcranial magnetic stimulation on the cerebellum of spinocerebellar degeneration patients Yasushi Hada a,*, Tatsuro Kaminaga b, Masahiro Mikami a a
Department of Rehabilitation Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi 173-8605, Tokyo, Japan b Department of Radiology, Teikyo University School of Medicine, Itabashi 173-8605, Tokyo, Japan
Abstract. In order to investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on the cerebellum of spinocerebellar degeneration (SCD) patients, the hemodynamic changes of the brain during rTMS was measured using noninvasive dynamic multi-channel near-infrared optical topography (OT). Two SCD patients diagnosed as OPCA participated in this study. Both had been having rTMS administered to their cerebellum once a week for more than 2 years for therapeutic purposes under the permission of the local ethical committee. Three sessions of 15 times application of 1 Hz rTMS were applied at 3-min intervals. OT probes were set on the scalp and the hemodynamic changes of the fronto-paretal lobe were measured during each session. Changes in hemoglobin were recorded at 15-s prestimulus intervals and consecutively 195 s during and after stimulus. Increased blood flow around the premotor area was observed during rTMS, and the effects were prolonged for more than at least a couple of minutes after rTMS. These results suggest that rTMS administered to the cerebellum of SCD patients may have a remote effect on the frontal lobe and that the blood flow of the frontal lobe may change during and after rTMS. D 2004 Elsevier B.V. All rights reserved. Keywords: Repetitive transcranial magnetic stimulation (rTMS); Spinocerebellar degeneration (SCD); Nearinfrared optical topography (OT); Remote effect
1. Introduction Transcranial magnetic stimulation (TMS) is used for treatment of such ailments as depression, Parkinson’s disease and dystonia as well as for research and diagnosis. TMS is also used as a treatment for spinocerebellar degeneration (SCD). Shimizu et al. [1] applied repetitive TMS (rTMS) to SCD patients and reported improvements in walking speed and body balance after 21 days.
* Corresponding author. Tel.: +81-3-3964-2597; fax: +81-3-3962-4087. E-mail address: [email protected] (Y. Hada). 0531-5131/ D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.ics.2004.04.030
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Y. Hada et al. / International Congress Series 1270 (2004) 233–236
We have two SCD patients who have undergone once-weekly rTMS over their cerebellum for more than 2 years, and no remarkable aggravation has been observed during this period. The efficacy and exact mechanisms of rTMS over the cerebellum of SCD patients still remain unclear, however. In addition to the direct effect on the cerebellum, remote effects like diaschisis to regions of the cerebral cortex, such as the primary motor cortex, premotor cortex and primary sensory cortex, may be involved. In order to investigate the effect of rTMS over the cerebellum of SCD patients, we measured the hemodynamic changes of the brain during and after rTMS using noninvasive dynamic multi-channel near-infrared optical topography (OT). 2. Material and methods/patients Two SCD patients formerly diagnosed as OPCA participated in this study. Both had been undergoing once-weekly rTMS to their cerebellum for more than 2 years under the permission of the local ethical committee. We used a magnetic stimulator SMN1200 (Nihon Kohden, Tokyo, Japan) with a 14-cm circular coil for rTMS. Maximum magnetic power of this stimulator was 0.51 T. Magnetic stimulations consisted of three sessions of 15 stimuli, with 3-min intervals. The center of the coil was held 5 cm left of the inion during the first session, 5 cm right of the inion during the second session, and at the inion during the third session. After every three stimuli, the coil at each position was turned over to change the direction of the current from clockwise to counter-clockwise or viceversa. We think that this method enabled us to give magnetic stimulations widely over the cerebellum. Because the purpose of this study was to investigate what occurs on the cerebral cortex during the rTMS that had been performed once weekly to SCD patients, we did not perform sham stimulations. In this experiment, we had 3-min intervals between sessions to observe the prolonged effect after stimulations. Stimulus intensity was as strong as possible without subjecting patients to discomfort. Near-infrared OT was performed using ETG-4000 (Hitachi Medical, Tokyo, Japan). A pair of 15 probes enabled us to monitor 22 channels (44 channels totally). Those two sets of probes were mounted on the scalp front parietally. The coronal center-line of those probes was adjusted to the C3-Cz-C4 line based on the EEG 10– 20 system, with 6-cm separation. Changes in hemoglobin were recorded at 15-s pre-stimulus intervals, 15 s during stimulation and for 180 consecutive seconds after stimulus. 3. Results Stimulus intensity was 80% of maximum power in subject 1 and 90% in subject 2. We obtained three sessions of OT images from each subject. Optical topography images of the first session of each subject are displayed in Figs. 1 and 2. These effects appeared during rTMS and were maintained after rTMS for a while, at least until the end of our observation. There were no side effects or complaints from the subjects during this experiment.
Y. Hada et al. / International Congress Series 1270 (2004) 233–236
Fig. 1. Optical topography of subject 1, first session. (A) Before rTMS, (B) during rTMS, (C) 3 min after rTMS. +, increment of total Hb; , decrement of total Hb (mM mm). An increase in total Hb was prominent at mid-lateral, frontcentral part of the right-hemisphere OT and at the center part of the left-hemisphere OT, during and after the first session of rTMS.
235
Fig. 2. Optical topography of subject 2, first session. (A) Before rTMS, (B) during rTMS, (C) 3 min after rTMS. +, increment of total Hb; , decrement of total Hb (mM mm). The increase of total Hb in the first session was prominent at the mid-medial part of the right-hemisphere OT, and at the central to medial part of the left-hemisphere OT. A decrease was prominent at the mid-lateral part of both hemispheres.
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Y. Hada et al. / International Congress Series 1270 (2004) 233–236
4. Discussion In the present study, positive and negative hemodynamic change was observed during and after rTMS over cerebellum. In the first session of subject 2, there seemed to exist a positive effect in the primary motor area and a negative effect in the premotor area; in that of subject 1, a positive effect existed in both the primary motor and premotor areas. However, we cannot argue about the cortical location in detail in the present study, because of a lack of information about the cortical map, TMS mapping and MRI linkages. Gerschlager et al. [2] reported that much of the persisting effects of rTMS over cerebellum on cortico-spinal excitability appear to be mediated through the stimulation of peripheral rather than central structures. We used a large diameter ring coil for stimulation in the present study, so that the stimulated area would be wide and vague. Hence, our stimulations might have affected not only the cerebellum but also peripheral structures and the occipital lobe. Enhancement and depression of cerebral blood flow through rTMS over cerebellum was prolonged for some time after rTMS, at least until the end of our observation in the present study. Chen et al. [3] found that 0.9 Hz rTMS on motor cortex decreased cortical excitability, and lasted for at least 15 min during the post-rTMS period. They thought that the depression they observed was mediated by long-term depression (LTD). Repetitive TMS over the cerebellum may create the same mechanisms as LTD and long-term potentiation, so we will need to observe the OT changes in a much longer post-rTMS period, using another experimental design accompanied with MRI and SPECT in the future. In conclusion, rTMS administered to the cerebellum of SCD patients may have a remote effect on the frontal lobe. The blood flow of the frontal and parietal cortex may be modulated by rTMS, and this effect may linger after rTMS. References [1] H. Shimizu, et al., Therapeutic efficacy of trans magnetic stimulation for hereditary spinocerebellar degeneration, Tohoku Journal of Experimental Medicine 189 (1999) 203 – 211. [2] W. Gerschlager, et al., rTMS over the cerebellum can increase corticospinal excitability through a spinal mechanism involving activation of peripheral nerve fibres, Clinical Neurophysiology 113 (9) (2002) 1435 – 1440. [3] R. Chen, et al., Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation, Neurology 48 (5) (1997) 1398 – 1403.
www.ics-elsevier.com
Remote effect of repetitive transcranial magnetic stimulation on the cerebellum of spinocerebellar degeneration patients Yasushi Hada a,*, Tatsuro Kaminaga b, Masahiro Mikami a a
Department of Rehabilitation Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi 173-8605, Tokyo, Japan b Department of Radiology, Teikyo University School of Medicine, Itabashi 173-8605, Tokyo, Japan
Abstract. In order to investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on the cerebellum of spinocerebellar degeneration (SCD) patients, the hemodynamic changes of the brain during rTMS was measured using noninvasive dynamic multi-channel near-infrared optical topography (OT). Two SCD patients diagnosed as OPCA participated in this study. Both had been having rTMS administered to their cerebellum once a week for more than 2 years for therapeutic purposes under the permission of the local ethical committee. Three sessions of 15 times application of 1 Hz rTMS were applied at 3-min intervals. OT probes were set on the scalp and the hemodynamic changes of the fronto-paretal lobe were measured during each session. Changes in hemoglobin were recorded at 15-s prestimulus intervals and consecutively 195 s during and after stimulus. Increased blood flow around the premotor area was observed during rTMS, and the effects were prolonged for more than at least a couple of minutes after rTMS. These results suggest that rTMS administered to the cerebellum of SCD patients may have a remote effect on the frontal lobe and that the blood flow of the frontal lobe may change during and after rTMS. D 2004 Elsevier B.V. All rights reserved. Keywords: Repetitive transcranial magnetic stimulation (rTMS); Spinocerebellar degeneration (SCD); Nearinfrared optical topography (OT); Remote effect
1. Introduction Transcranial magnetic stimulation (TMS) is used for treatment of such ailments as depression, Parkinson’s disease and dystonia as well as for research and diagnosis. TMS is also used as a treatment for spinocerebellar degeneration (SCD). Shimizu et al. [1] applied repetitive TMS (rTMS) to SCD patients and reported improvements in walking speed and body balance after 21 days.
* Corresponding author. Tel.: +81-3-3964-2597; fax: +81-3-3962-4087. E-mail address: [email protected] (Y. Hada). 0531-5131/ D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.ics.2004.04.030
234
Y. Hada et al. / International Congress Series 1270 (2004) 233–236
We have two SCD patients who have undergone once-weekly rTMS over their cerebellum for more than 2 years, and no remarkable aggravation has been observed during this period. The efficacy and exact mechanisms of rTMS over the cerebellum of SCD patients still remain unclear, however. In addition to the direct effect on the cerebellum, remote effects like diaschisis to regions of the cerebral cortex, such as the primary motor cortex, premotor cortex and primary sensory cortex, may be involved. In order to investigate the effect of rTMS over the cerebellum of SCD patients, we measured the hemodynamic changes of the brain during and after rTMS using noninvasive dynamic multi-channel near-infrared optical topography (OT). 2. Material and methods/patients Two SCD patients formerly diagnosed as OPCA participated in this study. Both had been undergoing once-weekly rTMS to their cerebellum for more than 2 years under the permission of the local ethical committee. We used a magnetic stimulator SMN1200 (Nihon Kohden, Tokyo, Japan) with a 14-cm circular coil for rTMS. Maximum magnetic power of this stimulator was 0.51 T. Magnetic stimulations consisted of three sessions of 15 stimuli, with 3-min intervals. The center of the coil was held 5 cm left of the inion during the first session, 5 cm right of the inion during the second session, and at the inion during the third session. After every three stimuli, the coil at each position was turned over to change the direction of the current from clockwise to counter-clockwise or viceversa. We think that this method enabled us to give magnetic stimulations widely over the cerebellum. Because the purpose of this study was to investigate what occurs on the cerebral cortex during the rTMS that had been performed once weekly to SCD patients, we did not perform sham stimulations. In this experiment, we had 3-min intervals between sessions to observe the prolonged effect after stimulations. Stimulus intensity was as strong as possible without subjecting patients to discomfort. Near-infrared OT was performed using ETG-4000 (Hitachi Medical, Tokyo, Japan). A pair of 15 probes enabled us to monitor 22 channels (44 channels totally). Those two sets of probes were mounted on the scalp front parietally. The coronal center-line of those probes was adjusted to the C3-Cz-C4 line based on the EEG 10– 20 system, with 6-cm separation. Changes in hemoglobin were recorded at 15-s pre-stimulus intervals, 15 s during stimulation and for 180 consecutive seconds after stimulus. 3. Results Stimulus intensity was 80% of maximum power in subject 1 and 90% in subject 2. We obtained three sessions of OT images from each subject. Optical topography images of the first session of each subject are displayed in Figs. 1 and 2. These effects appeared during rTMS and were maintained after rTMS for a while, at least until the end of our observation. There were no side effects or complaints from the subjects during this experiment.
Y. Hada et al. / International Congress Series 1270 (2004) 233–236
Fig. 1. Optical topography of subject 1, first session. (A) Before rTMS, (B) during rTMS, (C) 3 min after rTMS. +, increment of total Hb; , decrement of total Hb (mM mm). An increase in total Hb was prominent at mid-lateral, frontcentral part of the right-hemisphere OT and at the center part of the left-hemisphere OT, during and after the first session of rTMS.
235
Fig. 2. Optical topography of subject 2, first session. (A) Before rTMS, (B) during rTMS, (C) 3 min after rTMS. +, increment of total Hb; , decrement of total Hb (mM mm). The increase of total Hb in the first session was prominent at the mid-medial part of the right-hemisphere OT, and at the central to medial part of the left-hemisphere OT. A decrease was prominent at the mid-lateral part of both hemispheres.
236
Y. Hada et al. / International Congress Series 1270 (2004) 233–236
4. Discussion In the present study, positive and negative hemodynamic change was observed during and after rTMS over cerebellum. In the first session of subject 2, there seemed to exist a positive effect in the primary motor area and a negative effect in the premotor area; in that of subject 1, a positive effect existed in both the primary motor and premotor areas. However, we cannot argue about the cortical location in detail in the present study, because of a lack of information about the cortical map, TMS mapping and MRI linkages. Gerschlager et al. [2] reported that much of the persisting effects of rTMS over cerebellum on cortico-spinal excitability appear to be mediated through the stimulation of peripheral rather than central structures. We used a large diameter ring coil for stimulation in the present study, so that the stimulated area would be wide and vague. Hence, our stimulations might have affected not only the cerebellum but also peripheral structures and the occipital lobe. Enhancement and depression of cerebral blood flow through rTMS over cerebellum was prolonged for some time after rTMS, at least until the end of our observation in the present study. Chen et al. [3] found that 0.9 Hz rTMS on motor cortex decreased cortical excitability, and lasted for at least 15 min during the post-rTMS period. They thought that the depression they observed was mediated by long-term depression (LTD). Repetitive TMS over the cerebellum may create the same mechanisms as LTD and long-term potentiation, so we will need to observe the OT changes in a much longer post-rTMS period, using another experimental design accompanied with MRI and SPECT in the future. In conclusion, rTMS administered to the cerebellum of SCD patients may have a remote effect on the frontal lobe. The blood flow of the frontal and parietal cortex may be modulated by rTMS, and this effect may linger after rTMS. References [1] H. Shimizu, et al., Therapeutic efficacy of trans magnetic stimulation for hereditary spinocerebellar degeneration, Tohoku Journal of Experimental Medicine 189 (1999) 203 – 211. [2] W. Gerschlager, et al., rTMS over the cerebellum can increase corticospinal excitability through a spinal mechanism involving activation of peripheral nerve fibres, Clinical Neurophysiology 113 (9) (2002) 1435 – 1440. [3] R. Chen, et al., Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation, Neurology 48 (5) (1997) 1398 – 1403.