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Dec 7, 2012. Continuous Repetitive Transcranial Magnetic Stimulation for intractable Neuropathic Pain. Youichi Saitoh , M.D., Ph.D. Department of Neuromodulation and Neurosurgery Office for Univeristy -Industry Collaboration, Osaka University. - PowerPoint PPT Presentation
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Continuous Repetitive Transcranial Magnetic Stimulation for intractable
Neuropathic Pain
Youichi Saitoh, M.D., Ph.D.Department of Neuromodulation and Neurosurgery
Office for Univeristy-Industry Collaboration,Osaka University
Dec 7, 2012
Rasche et al., Pain, 2006
Electrical motor cortex stimulation; EMCS
Saitoh et al. J Neurosurg 2000Department of Neurosurgery, Osaka University Graduate School of Medicine
EMCS expand to the world from Japan
Efficacy of EMCS on intractable neuropathic pain
Saitoh and Yoshimine, Acta Neurochir Suppl, 2007
Approximately half of the patients satisfy
No large double-blinded clinical trials
Saitoh Y et al, Acta Neurochir, 2007
Repetitive transcranial magnetic stimulation (rTMS)
Eddy currentFigure-8-coil is most popular
curent
Cochrane reviewO’Connell NE et al, 2010Non-invasive brain stimulation techniques for chronic pain
Single doses of high-frequency rTMS of motor cortex may have short-term effects on chronic pain.
Efficacies of cranial electrotherapy stimulation and transcranial direct current stimulation are uncertain.
VS
Multi-centered, Randomized, double-blind, sham-controlled, crossover study
2009 〜 2011
This study was funded by the Japanese Ministry of Health, Labour and Welfare with a Health and Labour Sciences Research Grant.
Randomized, double-blind, sham-controlled, crossover study
Real (5Hz) and sham stimulations are randomized.Double-blind Randomized Crossover StudySpecialist of biological statistics randomized the patients to two
groups.Validation of efficacy and safety of daily rTMS for 2 weeks.
Previous studies were mostly single sessionPrimary endpoint is VAS, secondary is SF-MPQ
Realistic sham is applied.Synchronized cutaneous electrical stimulation is delivered.Hamada M et al, Mov Disord, 23:1524-31, 2008
70 patients
Randomized, double-blind, sham-controlled, crossover study
Seven centersRehabilitation, Hokaido Univ.Neurology, FukushimaNeurosurgery, Nihon Univ.Neurosurgery, Hamamatsu Univ.Neurosurgery, Osaka Univ.Neurology, Kinki Univ.Neurology, Univ. of Occulational
Protocol of sham-controlled crossover study Observati
on Intervention Observation
day 1 2 3 4 5 6~ 7 8 9 10 11 12 13 ~14 15 16 ~
21 22 23 ~28 29
Examination □ □ □ □ □ □ □ □ □ □ □ □ □ □rTMS ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆ ◆
Agreement ○Background ○
MRI/EEG ○Subjective signObjective sign ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○Adverse effect ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○
VAS ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○SF-MPQ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○
BDI ○ ○ ○ ○ ○ ○PGIC ○ ○ ○ ○ ○ ○
VAS, Visual analogue scale; SF-MPQ, short form of McGill pain questionnaire; BDI, Beck depression inventry
Trial profileSham firstReal first
Results of short-term effect of VASPrimary endpoint
-2
0
2
4
6
8
10
12Group A (Real) Group A (Sham)
Group B (Real) Group B (Sham)
Day
VA
S re
duct
ion
rate
% (S
EM)
1 2 3 4 5 8 9 10 11 12 1 2 3 4 5 8 9 10 11 12
First period
First week Second week First week Second week
Second period
Results of short-term effect of SF-MPQ Secondary endpoint
0
5
10
15
20
25 Group A (Real) Group A (Sham)
Group B (Real) Group B (Sham)
Day
SF-M
PQ re
duct
ion
rate
% (S
EM)
1 2 3 4 5 8 9 10 11 12 1 2 3 4 5 8 9 10 11 12
First period
First week Second week First week Second week
Second period
1 2 3 4 5 8 9 10 11 12 1 2 3 4 5 8 9 10 11 12
First period
First week Second week First week Second week
Second period
Patient global impression of change (PGIC)
Intervention
Beck depression inventory (BDI)
Intervention
Number of patients Number of
respondersMean efficacy
rate (%)
[95% CI] Interaction p
value Sex Male 39 9 23 [ 10.6 - 31.8 ] 0.509
Female 22 3 13.6 [ 2.9 - 34.9 ] Age [ - ] <60 24 6 25 [ 9.8 - 46.7 ] 0.513
≥60 37 6 16.2 [ 6.2 - 32 ] Underlying disease [ - ] Cerebral lesion 50 10 20 [ 10 - 33.7 ] 1
Non-cerebral lesion 11 2 18.2 [ 2.3 - 51.8 ] Lesion site [ - ] Thalamus 28 3 10.7 [ 2.3 - 28.2 ] 0.14
Lenticular nucleus 17 6 35.3 [ 14.2 - 61.7 ] Others 16 3 18.8 [ 4 - 45.6 ] Treated painful region [ - ] Face 6 1 16.7 [ 0.4 - 64.1 ] 0.588
Upper limb 32 8 25 [ 11.4 - 43.4 ] Lower limb 23 3 13 [ 2.7 - 33.6 ] Pain laterality [ - ] Left 27 6 22.2 [ 8.6 - 42.2 ] 0.407
Right 34 11 17.6 [ 6.8 - 34.5 ] Previous treatment [ - ] Medication alone 43 9 20.9 [ 10 - 36 ] 1
Block 12 2 16.7 [ 2.1 - 48.4 ] Others 6 1 16.7 [ 0 - 64.1 ] Efficacy rate (%)
Figure 6: Forest plot of subgroup analyses
Short-term efficacy rate (VAS reduction rate subtracting sham of ≥10%) of each subgroup was shown. 95% CIs were calculated by exact binominal method.
0 10 20 30 40 50 60 70 80
Forest Plot of subgroup analyses
Adverse effects
DiscussionThis prospective study shows daily high-frequency rTMS is
transiently effective for pain relief in intractable neuropathic pain patients (70 cases).
There has been no serious adverse effects.The real rTMS, compared with the sham, showed significant
short-term improvements in VAS and SF-MPQ scores without a carry-over effect. The result of PGIC suggested cumulative effect.
More than once a day or continuous rTMS treatment may improve the effect.
In this study, 81% of enrolled patients were post-stroke pain and 60.7 y.o. (mean) which is older than previous studies. Therefore, the effect was mild but significant.
PFC
rTMS
M1
Th
S2
InsPAG
ACCModulate pain recognition
Pain relief
Elicit plastic changes
Cerebral mechanism of pain relief(EMCS, rTMS)
Modulate a pain threshold
Thank you for attention!!