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Therapeutic efficacy of transcranial magnetic stimulation for amyotrophic lateral sclerosis and spinocerebellar degeneration
International Congress Series 1235 (2002) 525 – 532
Therapeutic efficacy of transcranial magnetic stimulation for amyotrophic lateral sclerosis and spinocerebellar degeneration Masahiro Horiuchi a,*, Futaba Maki a, Toshiyuki Yanagisawa a, Hiroshi Sugihara a, Yoichi Takahashi a, Kenjiro Ohashi b, Kaoru Sasaka b, Yasuo Nakajima b a
Division of Neurology, Department of Internal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8511, Japan b Department of Radiology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8511, Japan
Abstract We treated four patients with amyotrophic lateral sclerosis (ALS) and nine patients with spinocerebellar degeneration (SCD) using transcranial magnetic stimulation (TMS) with an SMN1200 transcranial magnetic stimulator. The stimulus strength was below 1.5 T and the interpulse interval was greater than 5 s. The stimulus coil was placed on P3, P4 and the bilateral cervical and lumbar root in the ALS patients, and tangentially over Iz, 4 cm lateral to the right from Iz and 4 cm lateral to the left from Iz in the SCD patients. Ten consecutive pulses were delivered to each region in the ALS patients and 15 in the SCD patients. Transcranial magnetic stimulation (TMS) was applied for a total of 20 days for in-patients and once or twice a week as ongoing therapy for outpatients. Patients with ALS were assessed according to the Barthel index, and a respiratory function test was performed before and after TMS. Patients with SCD were neurologically assessed according to the International Cooperative Ataxia Rating Scale (ICARS). In addition, the patients were evaluated for regional cerebral blood flow (rCBF) by 99 m Tc-ECD SPECT using a modified Patlak-plot method before and after the TMS trial. No change in the Barthel index or rCBF was observed in patients with ALS. The respiratory function test results improved in one patient in the ALS group. The ICARS rating of seven
*
Corresponding author. Tel.: +81-44-977-8111; fax: +81-44-976-8516. E-mail address: [email protected] (M. Horiuchi).
0531-5131/02 D 2002 Elsevier Science B.V. All rights reserved. PII: S 0 5 3 1 - 5 1 3 1 ( 0 2 ) 0 0 2 4 2 - X
526
M. Horiuchi et al. / International Congress Series 1235 (2002) 525–532
patients with SCD improved after TMS. The rCBF of patients with SCD in the bilateral cerebellar hemispheres was significantly faster compared to their flow rate before TMS. These data suggest the potential usefulness of TMS as a therapeutic tool for ALS and SCD. D 2002 Elsevier Science B.V. All rights reserved. Keywords: Transcranial magnetic stimulation; Amyotrophic lateral sclerosis; Spinocerebellar degeneration; Regional cerebral blood flow
1. Background Transcranial magnetic stimulation (TMS) has been shown to have clear clinical benefits for depression, Parkinson’s disease [1] and SCD [2]. We performed TMS therapy for patients with amyotrophic lateral sclerosis (ALS) and spinocerebellar degeneration (SCD).
2. Methods Four patients (60.8F3.7 years old) (Table 1) with ALS and nine patients with SCD (55.8F11.3 years old) (Table 2) were enrolled in this study. The transcranial magnetic stimulator was an SMN-1200 (Nihon-koden, Tokyo) model with a 14.1-cm circular coil. The stimulus strength was below 1.5 T and the interpulse interval greater than 5 s. The stimulus coil was placed on P3, P4 (international 10– 20 system) and the bilateral cervical and lumbar root in the ALS patients and tangentially over Iz, 4 cm lateral to the right from Iz and 4 cm lateral to the left from Iz in the SCD patients. Ten consecutive pulses were delivered to each region in the ALS patients and 15 to the SCD patients. Transcranial magnetic stimulation (TMS) was performed for a total of 20 days for the in-patients and as ongoing therapy at once or twice a week for the outpatients. Patients with ALS were assessed according to the Barthel index [3] and a respiratory function test was performed before and after TMS. Patients with SCD were neurologically assessed according to the International Cooperative Ataxia Rating Scale (ICARS) [4]. The regional cerebral blood flow (rCBF) was evaluated in patients with ALS in the bilateral frontal lobes, and in patients with SCD in the bilateral cerebellar hemispheres, and pontine base by 99 m Tc-ECD SPECT using a modified Patlak-plot method both before and after the TMS trial.
3. Results No change in the Barthel index or rCBF was observed in the ALS patients. The respiratory function test results of patient 4 in the ALS group improved after TMS (Fig. 1).
No. Age Sex Diagnosis Onset
Group
Start of TMS
Barthel index (points) Before
1
58
F
2
58
F
ALS (bulbar) ALS
3
60
F
ALS
4
67
F
ALS
August 1999 February 2000 July 1999 July 2000
Out to September 80 In to Out 2000 Out-patient November 45 2000 Out-patient October 30 2000 In to Out December 85 to In 2000
rCBF (before)
Right frontal lobe (ml/100 g/min)
Left rCBF frontal (after) lobe (ml/100 g/min)
Right frontal lobe (ml/100 g/min)
Left Medicine frontal lobe (ml/100 g/min)
5 October 2000 9 November 2000 5 October 2000 22 November 2000
49.75
45.15
50.19
40.55
59.82
56.3
57.78
52.97
Riruzole
48.62
54.36
53.73
57.54
Riruzole
57.33
60.66
60.62
61.59
After
80 45 30 70
16 November 2000 25 January 2001 7 December 2000 14 December 2000
M. Horiuchi et al. / International Congress Series 1235 (2002) 525–532
Table 1
527
528
M. Horiuchi et al. / International Congress Series 1235 (2002) 525–532
Table 2 No.
Age
Sex
Diagnosis
Onset
Group
Start of TMS
Improvement of ICARS
Before (points)
After
1
53
F
OPCA
1998
In-patient
Dysarthria
67
65
2
67
F
OPCA
1995
Outpatient
65
65
3
65
M
OPCA
1998
In-patient
53
52
4
61
F
OPCA
1998
In to Out
40
38
5
36
M
MJD
1986
In to Out
September 2000 November 2000 October 2000 December 2000 October 2000
34
29
6
54
F
SCA6
1984
Outpatient
40
40
7
37
M
MJD
1986
In-patient
28
20
8
65
M
OPCA
1998
In-patient
February 2001
40
37
9
64
F
SCA6
1992
In-patient
February 2001
49
40
December 2000 February 2001
Truncal ataxia Dysarthria Gait disturbance, nystagmus
Gait disturbance, dysarthria Gait disturbance, ataxia Gait disturbance, ataxia, dysarthria, nystagmus
The ICARS rating of seven patients with SCD improved after TMS (Fig. 2). The rCBF of patients with SCD in the bilateral cerebellar hemispheres was higher than before TMS (Fig. 3).
4. Discussion In Parkinson’s disease patients, Davis et al. [5] assessed the changes in rCBF and Parkinsonian symptoms during disruption of globus pallidus (GPi) activity with high frequency stimulation delivered through implanted brain electrodes. Positron emission tomography (PET) revealed an increase in rCBF in ipsilateral premotor cortical areas, which improved rigidity and bradykinesia. These results suggest that disrupting excessive inhibitory input of the basal ganglia reverses Parkinsonism, via a thalamic relay, by activation of brain areas involved in the initiation of movement. In the present study, the respiratory function test result of patient 4 in the ALS group improved after TMS, suggesting that TMS may be an effective therapy for patients with ALS. The underlying mechanism responsible for this improvement remains to be determined.
M. Horiuchi et al. / International Congress Series 1235 (2002) 525–532
529
rCBF (before)
Right cerebellum (ml/100 g/min)
Left Pontine rCBF cerebellum base (after) (ml/100 g/min)
Right cerebellum (ml/100 g/min)
Left Pontine Medicine cerebellum base (ml/100 g/min)
7 September 2000 9 November 2000 19 October 20000 30 November 2000 20 December 2000
40.62
43.6
37.51
41.28
Ceredist
47.16
42.28
47.25
47.79
Ceredist
39.83
39.77
45.14
43.89
Ceredist
49.45
47.05
50.88
51.77
Ceredist
63.24
60.08
68.46
72.95
14 December 60.19 2000 31 January 52.64 2001
59.34
21 March 2001 25 January 2001 7 February 2001 20 December 2000 22 February 2001 22 February 2001 21 March 2001
63.51
67.13
Ceredist
59.24
63.91
Ceredist
15 February 2001
47.45
46.34
14 March 2001
45.6
41.26
21 February 2001
56.69
62.77
15 March 2001
66.97
63.77
39.27
53.8
40.54
54.25
27.78
Ceredist
Ceredist
Hirtonin
The rCBF of the cerebellar hemisphere of patients with SCD significantly increased during the TMS trial. Transcranial magnetic stimulation (TMS) improved the microcirculation of the brain with accompanying clinical improvements. Although the exact mechanism by which TMS improved ataxia remains unknown, we speculate that increased blood flow in the cerebellum played a role in this improvement.
5. Conclusions These findings indicate the potential usefulness of TMS as a therapeutic tool for ALS and SCD.
References [1] H. Shimamoto, M. Shigemori, Therapeutic effect of repetitive transcranial magnetic stimulation on Parkinson disease, Neurol. Med. 51 (1999) 419 – 425.
530 M. Horiuchi et al. / International Congress Series 1235 (2002) 525–532
Fig. 1. The respiratory function test results of Patient 4 in the ALS group improved following TMS therapy.
M. Horiuchi et al. / International Congress Series 1235 (2002) 525–532
531
Fig. 2. The ICARS rating of seven patients with SCD improved after TMS.
Fig. 3. The rCBF of patients with SCD in the bilateral cerebellar hemispheres was higher compared to before TMS.
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M. Horiuchi et al. / International Congress Series 1235 (2002) 525–532
[2] H. Shimizu, T. Tsuda, Y. Shiga, K. Miyazawa, Y. Onodera, M. Matsuzaki, M. Nakashima, K. Furukawa, M. Aoki, H. Kato, T. Yamazaki, Y. Itoyama, Therapeutic efficacy of transcranial magnetic stimulation for hereditary spinocerebellar degeneration, Tohoku J. Exp. Med. 189 (1999) 203 – 211. [3] F.I. Mahoney, D.W. Barthel, Functional evaluation: the Barthel index, Maryland St. Med. J. 14 (1965) 61 – 65. [4] P. Trouillas, T. Takayanagi, M. Hallet, R.D. Currier, S.H. Subramony, K. Wessel, A. Bryer, H.C. Diener, S. Massaquoi, C.M. Gomez, P. Coutinho, M.B. Hamida, G. Campanella, A. Filla, L. Schut, D. Tiemann, J. Honnorat, N. Nighoghossian, B. Manyam, International cooperative ataxia rating scale for pharmacological assessment of cerebellar syndrome, J. Neurol. Sci. 145 (1997) 205 – 211. [5] K.D. Davis, E. Taub, S. Houle, A.E. Lang, J.O. Dostrovsky, R.R. Tasker, A.M. Lozano, Globus pallidus stimulation activities the cortical motor system during alleviation of Parkinsonian symptoms, Nat. Med. 3 (1997) 671 – 674.
Therapeutic efficacy of transcranial magnetic stimulation for amyotrophic lateral sclerosis and spinocerebellar degeneration Masahiro Horiuchi a,*, Futaba Maki a, Toshiyuki Yanagisawa a, Hiroshi Sugihara a, Yoichi Takahashi a, Kenjiro Ohashi b, Kaoru Sasaka b, Yasuo Nakajima b a
Division of Neurology, Department of Internal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8511, Japan b Department of Radiology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8511, Japan
Abstract We treated four patients with amyotrophic lateral sclerosis (ALS) and nine patients with spinocerebellar degeneration (SCD) using transcranial magnetic stimulation (TMS) with an SMN1200 transcranial magnetic stimulator. The stimulus strength was below 1.5 T and the interpulse interval was greater than 5 s. The stimulus coil was placed on P3, P4 and the bilateral cervical and lumbar root in the ALS patients, and tangentially over Iz, 4 cm lateral to the right from Iz and 4 cm lateral to the left from Iz in the SCD patients. Ten consecutive pulses were delivered to each region in the ALS patients and 15 in the SCD patients. Transcranial magnetic stimulation (TMS) was applied for a total of 20 days for in-patients and once or twice a week as ongoing therapy for outpatients. Patients with ALS were assessed according to the Barthel index, and a respiratory function test was performed before and after TMS. Patients with SCD were neurologically assessed according to the International Cooperative Ataxia Rating Scale (ICARS). In addition, the patients were evaluated for regional cerebral blood flow (rCBF) by 99 m Tc-ECD SPECT using a modified Patlak-plot method before and after the TMS trial. No change in the Barthel index or rCBF was observed in patients with ALS. The respiratory function test results improved in one patient in the ALS group. The ICARS rating of seven
*
Corresponding author. Tel.: +81-44-977-8111; fax: +81-44-976-8516. E-mail address: [email protected] (M. Horiuchi).
0531-5131/02 D 2002 Elsevier Science B.V. All rights reserved. PII: S 0 5 3 1 - 5 1 3 1 ( 0 2 ) 0 0 2 4 2 - X
526
M. Horiuchi et al. / International Congress Series 1235 (2002) 525–532
patients with SCD improved after TMS. The rCBF of patients with SCD in the bilateral cerebellar hemispheres was significantly faster compared to their flow rate before TMS. These data suggest the potential usefulness of TMS as a therapeutic tool for ALS and SCD. D 2002 Elsevier Science B.V. All rights reserved. Keywords: Transcranial magnetic stimulation; Amyotrophic lateral sclerosis; Spinocerebellar degeneration; Regional cerebral blood flow
1. Background Transcranial magnetic stimulation (TMS) has been shown to have clear clinical benefits for depression, Parkinson’s disease [1] and SCD [2]. We performed TMS therapy for patients with amyotrophic lateral sclerosis (ALS) and spinocerebellar degeneration (SCD).
2. Methods Four patients (60.8F3.7 years old) (Table 1) with ALS and nine patients with SCD (55.8F11.3 years old) (Table 2) were enrolled in this study. The transcranial magnetic stimulator was an SMN-1200 (Nihon-koden, Tokyo) model with a 14.1-cm circular coil. The stimulus strength was below 1.5 T and the interpulse interval greater than 5 s. The stimulus coil was placed on P3, P4 (international 10– 20 system) and the bilateral cervical and lumbar root in the ALS patients and tangentially over Iz, 4 cm lateral to the right from Iz and 4 cm lateral to the left from Iz in the SCD patients. Ten consecutive pulses were delivered to each region in the ALS patients and 15 to the SCD patients. Transcranial magnetic stimulation (TMS) was performed for a total of 20 days for the in-patients and as ongoing therapy at once or twice a week for the outpatients. Patients with ALS were assessed according to the Barthel index [3] and a respiratory function test was performed before and after TMS. Patients with SCD were neurologically assessed according to the International Cooperative Ataxia Rating Scale (ICARS) [4]. The regional cerebral blood flow (rCBF) was evaluated in patients with ALS in the bilateral frontal lobes, and in patients with SCD in the bilateral cerebellar hemispheres, and pontine base by 99 m Tc-ECD SPECT using a modified Patlak-plot method both before and after the TMS trial.
3. Results No change in the Barthel index or rCBF was observed in the ALS patients. The respiratory function test results of patient 4 in the ALS group improved after TMS (Fig. 1).
No. Age Sex Diagnosis Onset
Group
Start of TMS
Barthel index (points) Before
1
58
F
2
58
F
ALS (bulbar) ALS
3
60
F
ALS
4
67
F
ALS
August 1999 February 2000 July 1999 July 2000
Out to September 80 In to Out 2000 Out-patient November 45 2000 Out-patient October 30 2000 In to Out December 85 to In 2000
rCBF (before)
Right frontal lobe (ml/100 g/min)
Left rCBF frontal (after) lobe (ml/100 g/min)
Right frontal lobe (ml/100 g/min)
Left Medicine frontal lobe (ml/100 g/min)
5 October 2000 9 November 2000 5 October 2000 22 November 2000
49.75
45.15
50.19
40.55
59.82
56.3
57.78
52.97
Riruzole
48.62
54.36
53.73
57.54
Riruzole
57.33
60.66
60.62
61.59
After
80 45 30 70
16 November 2000 25 January 2001 7 December 2000 14 December 2000
M. Horiuchi et al. / International Congress Series 1235 (2002) 525–532
Table 1
527
528
M. Horiuchi et al. / International Congress Series 1235 (2002) 525–532
Table 2 No.
Age
Sex
Diagnosis
Onset
Group
Start of TMS
Improvement of ICARS
Before (points)
After
1
53
F
OPCA
1998
In-patient
Dysarthria
67
65
2
67
F
OPCA
1995
Outpatient
65
65
3
65
M
OPCA
1998
In-patient
53
52
4
61
F
OPCA
1998
In to Out
40
38
5
36
M
MJD
1986
In to Out
September 2000 November 2000 October 2000 December 2000 October 2000
34
29
6
54
F
SCA6
1984
Outpatient
40
40
7
37
M
MJD
1986
In-patient
28
20
8
65
M
OPCA
1998
In-patient
February 2001
40
37
9
64
F
SCA6
1992
In-patient
February 2001
49
40
December 2000 February 2001
Truncal ataxia Dysarthria Gait disturbance, nystagmus
Gait disturbance, dysarthria Gait disturbance, ataxia Gait disturbance, ataxia, dysarthria, nystagmus
The ICARS rating of seven patients with SCD improved after TMS (Fig. 2). The rCBF of patients with SCD in the bilateral cerebellar hemispheres was higher than before TMS (Fig. 3).
4. Discussion In Parkinson’s disease patients, Davis et al. [5] assessed the changes in rCBF and Parkinsonian symptoms during disruption of globus pallidus (GPi) activity with high frequency stimulation delivered through implanted brain electrodes. Positron emission tomography (PET) revealed an increase in rCBF in ipsilateral premotor cortical areas, which improved rigidity and bradykinesia. These results suggest that disrupting excessive inhibitory input of the basal ganglia reverses Parkinsonism, via a thalamic relay, by activation of brain areas involved in the initiation of movement. In the present study, the respiratory function test result of patient 4 in the ALS group improved after TMS, suggesting that TMS may be an effective therapy for patients with ALS. The underlying mechanism responsible for this improvement remains to be determined.
M. Horiuchi et al. / International Congress Series 1235 (2002) 525–532
529
rCBF (before)
Right cerebellum (ml/100 g/min)
Left Pontine rCBF cerebellum base (after) (ml/100 g/min)
Right cerebellum (ml/100 g/min)
Left Pontine Medicine cerebellum base (ml/100 g/min)
7 September 2000 9 November 2000 19 October 20000 30 November 2000 20 December 2000
40.62
43.6
37.51
41.28
Ceredist
47.16
42.28
47.25
47.79
Ceredist
39.83
39.77
45.14
43.89
Ceredist
49.45
47.05
50.88
51.77
Ceredist
63.24
60.08
68.46
72.95
14 December 60.19 2000 31 January 52.64 2001
59.34
21 March 2001 25 January 2001 7 February 2001 20 December 2000 22 February 2001 22 February 2001 21 March 2001
63.51
67.13
Ceredist
59.24
63.91
Ceredist
15 February 2001
47.45
46.34
14 March 2001
45.6
41.26
21 February 2001
56.69
62.77
15 March 2001
66.97
63.77
39.27
53.8
40.54
54.25
27.78
Ceredist
Ceredist
Hirtonin
The rCBF of the cerebellar hemisphere of patients with SCD significantly increased during the TMS trial. Transcranial magnetic stimulation (TMS) improved the microcirculation of the brain with accompanying clinical improvements. Although the exact mechanism by which TMS improved ataxia remains unknown, we speculate that increased blood flow in the cerebellum played a role in this improvement.
5. Conclusions These findings indicate the potential usefulness of TMS as a therapeutic tool for ALS and SCD.
References [1] H. Shimamoto, M. Shigemori, Therapeutic effect of repetitive transcranial magnetic stimulation on Parkinson disease, Neurol. Med. 51 (1999) 419 – 425.
530 M. Horiuchi et al. / International Congress Series 1235 (2002) 525–532
Fig. 1. The respiratory function test results of Patient 4 in the ALS group improved following TMS therapy.
M. Horiuchi et al. / International Congress Series 1235 (2002) 525–532
531
Fig. 2. The ICARS rating of seven patients with SCD improved after TMS.
Fig. 3. The rCBF of patients with SCD in the bilateral cerebellar hemispheres was higher compared to before TMS.
532
M. Horiuchi et al. / International Congress Series 1235 (2002) 525–532
[2] H. Shimizu, T. Tsuda, Y. Shiga, K. Miyazawa, Y. Onodera, M. Matsuzaki, M. Nakashima, K. Furukawa, M. Aoki, H. Kato, T. Yamazaki, Y. Itoyama, Therapeutic efficacy of transcranial magnetic stimulation for hereditary spinocerebellar degeneration, Tohoku J. Exp. Med. 189 (1999) 203 – 211. [3] F.I. Mahoney, D.W. Barthel, Functional evaluation: the Barthel index, Maryland St. Med. J. 14 (1965) 61 – 65. [4] P. Trouillas, T. Takayanagi, M. Hallet, R.D. Currier, S.H. Subramony, K. Wessel, A. Bryer, H.C. Diener, S. Massaquoi, C.M. Gomez, P. Coutinho, M.B. Hamida, G. Campanella, A. Filla, L. Schut, D. Tiemann, J. Honnorat, N. Nighoghossian, B. Manyam, International cooperative ataxia rating scale for pharmacological assessment of cerebellar syndrome, J. Neurol. Sci. 145 (1997) 205 – 211. [5] K.D. Davis, E. Taub, S. Houle, A.E. Lang, J.O. Dostrovsky, R.R. Tasker, A.M. Lozano, Globus pallidus stimulation activities the cortical motor system during alleviation of Parkinsonian symptoms, Nat. Med. 3 (1997) 671 – 674.