PANDUAN DISKUSI WORKSHOP TMS

AGUS SOLICHIEN, MD

Therapeutic Use of High-Frequency Repetitive Transcranial Magnetic Stimulation in Stroke

1. Christophe Hotermans, MD + Author Affiliations 1. Neurology Department, University of Lige, Lige, Belgium 1. Philippe Peigneux, PhD + Author Affiliations 1. Cyclotron Research Centre, University of Lige, Lige, Belgium 1. Gustave Moonen, MD, PhD; 2. Alain Maertens de Noordhout, MD, PhD; 3. Pierre Maquet, MD, PhD + Author Affiliations 1. Neurology Department, University of Lige, Lige, Belgium To the Editor: We read with great interest the article published by Kim et al on repetitive transcranial magnetic stimulation (rTMS)induced corticomotor excitability and associated motor skill acquisition in chronic stroke.1 The authors used high-frequency (10 Hz) rTMS over the primary motor cortex contralateral to the paretic hand in patients with chronic subcortical stroke and reported an immediate enhancement of excitability associated with an improvement in motor skill of the paretic hand. The induced enhancement of corticomotor excitability and the related improvement in performance open new and fascinating possibilities for future rehabilitation strategies. Despite our genuine enthusiasm for this kind of initiative, we feel that the effects of highfrequency rTMS still have to be firmly established and better understood, before it is proposed for widespread clinical use. First, the effect of rTMS is dependent on the frequency, intensity, intervals and duration of stimulation. At high frequency (>1 Hz), the effects on corticomotor excitability are highly

variable across subjects.2 Some healthy subjects even do not show any significant enhancement of corticospinal excitability after 10 Hz stimulation (although admittedly with other parameters of stimulation than those used by Kim et al).3 An even greater variability is to be expected in disease. This implies that in the context of the rehabilitation of stroke patients, the stimulation protocol will probably have to be tailored to each individual case. Second, high-frequency rTMS may worsen motor skill in healthy volunteers.4 We used in healthy volunteers high-frequency (20 Hz) rTMS with an intensity of 90% of resting motor threshold, during 20 minutes with trains of stimulation of 2 seconds and intertrain intervals of 28 seconds. Immediately after rTMS, subjects had a significantly lower performance on a finger-tapping task than controls (without rTMS). Third, rTMS effects may be temporary and unrelated to the motor performance eventually achieved in the long term. In our case, the detrimental effect of high-frequency rTMS was transient and the performance was similar 2 days later whether or not subjects had previously received rTMS. In patients, multiple sessions of rTMS5,6 would probably have to be performed to promote cortical plasticity and to induce a long-lasting functional recovery after stroke. Fourth, there are so far no safety guidelines for the use of rTMS in pathological conditions. For safety and methodological reasons, the authors restricted their study to subcortical stroke patients. Nevertheless, because of a higher motor threshold,1,7 these patients required a higher intensity of stimulation to enhance corticomotor excitability. This increases the risk of seizures and rTMS can become painful. Finally, low-frequency rTMS, which is typically better tolerated and safer, has also been shown to improve motor performance of the paretic hand when applied on the unaffected hemisphere.6,8,9 The respective risks and benefits of low- and high-frequency rTMS should be further specified.

Repetitive Transcranial Magnetic Stimulation of Contralesional Primary Motor Cortex Improves Hand Function After Stroke
1. 2. 3. 4. 5. Naoyuki Takeuchi, MD; Takayo Chuma, MD; Yuichiro Matsuo, MD; Ichiro Watanabe, MD, PhD; Katsunori Ikoma, MD, PhD

+ Author Affiliations

1. From the Department of Rehabilitation Medicine, Hokkaido University Graduate School of Medicine, Sapporo 060-0814, Japan. 1. Correspondence to Naoyuki Takeuchi, MD, Department of Rehabilitation Medicine, Hokkaido University Graduate School of Medicine, North 14 West 5, Sapporo 0600814, Japan. E-mail naoyuki@med.hokudai.ac.jp

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Abstract
Background and Purpose A recent report has demonstrated that the contralesional primary motor cortex (M1) inhibited the ipsilesional M1 via an abnormal transcallosal inhibition (TCI) in stroke patients. We studied whether a decreased excitability of the contralesional M1 induced by 1 Hz repetitive transcranial magnetic stimulation (rTMS) caused an improved motor performance of the affected hand in stroke patients by releasing the TCI. Methods We conducted a double-blind study of real versus sham rTMS in stroke patients. After patients had well- performed motor training to minimize the possibility of motor training during the motor measurement, they were randomly assigned to receive a subthreshold rTMS at the contralesional M1 (1 Hz, 25 minutes) or sham stimulation. Results When compared with sham stimulation, rTMS reduced the amplitude of motorevoked potentials in contralesional M1 and the TCI duration, and rTMS immediately induced an improvement in pinch acceleration of the affected hand, although a plateau in motor performance had been reached by the previous motor training. This improvement in motor function after rTMS was significantly correlated with a reduced TCI duration. Conclusions We have demonstrated that a disruption of the TCI by the contralesional M1 virtual lesion caused a paradoxical functional facilitation of the affected hand in stroke patients; this suggests a new neurorehabilitative strategy for stroke patients.

Therapeutic and dose-dependent effect of repetitive microelectroshock induced by transcranial magnetic stimulation in Parkinson's disease
1. Judit Mally1,*, 2. T. W. Stone2 Article first published online: 30 AUG 1999

Abstract
Transcranial magnetic stimulation (TMS) has been used in the diagnosis of neurological lesions and has been introduced into the therapy of central nervous diseases. Lately it has been claimed that TMS would be useful not only in the treatment of depression, but also in relieving symptoms of Parkinson's disease. In this study, we sought evidence of the effect of repetitive TMS on the symptoms of Parkinson's disease, the dose dependency between the applied elecromagnetic field and the Parkinsonian symptoms, and the maintenance of the improvement. Forty-nine patients with Parkinson's disease were divided into four groups, each given one stimulus, repeated 30 times, once or twice a day (0.34Tesla (T), 0.57T, 0.80T). Patients were followed for 3 months and assessed using two different parkinsonian scales: the graded clinical rating scale and Unified Parkinson Disability Rating Scale (UPDRS), and with a short-term memory test (Ziehen-Ranschburg word pair test). No effect was seen in the group treated with 0.34T\30 stimuli once a day. In all of the groups receiving TMS twice a day, the parkinsonian scores were significantly decreased compared with that of baselines after 1 month of treatment. The greatest improvement in the hypokinesia was detected in the group treated with 0.57T\30 stimuli twice a day (baseline total UPDRS: 30.62 15.23; 1 month after treatment: 17.08 7.04, P < 0.01; 3 months after treatment: 16.08 7.06, P < 0.01). A dose-dependent difference was observed between the two groups after 3 months. The total UPDRS in Group II (0.34T\30 stimuli twice a day) significantly differed from Group III (0.57T\30 stimuli twice a day; 22.43 8.87, 16.08 7.06, P < 0.05). The long-lasting improvement effect with TMS would seem to suggest it as an appropriate tool in the therapy of Parkinson's disease. J. Neurosci. Res. 57:935940, 1999. 1999 Wiley-Liss, Inc. Get PDF (84K)

Therapeutic effect and mechanism of repetitive transcranial magnetic stimulation in Parkinson's disease
Hotetsu Shimamoto, Katsuyuki Takasaki, Minoru Shigemori, Toshihiro Imaizumi, Mitsuyoshi Ayabe and Hiroshi Shoji

Abstract
The therapeutic effect of repetitive transcranial magnetic stimulation (rTMS) on clinical performance was assessed by a double-blind study in 9 patients with Parkinson's disease (PD). Nine other patients underwent sham stimulation as controls. The modified Hoehn and Yahr (H&Y) staging scale, the Schwab and England Activities of Daily Living (ADL) scale, and the Unified Parkinson's disease rating scale (UPDRS) were used to assess changes of clinical performance. Patients were assessed prior to and following 2 months of rTMS. In addition, the mechanism of rTMS was investigated by dopamine and homovanillic acid (HVA) in the lumbar cerebrospinal fluid (CSF) of 17 patients before and after therapeutic rTMS for three or four months. rTMS was applied manually to the frontal areas 60 times per session, i. e., 30 times per side using a large circular coil, a pulse intensity of 700 V, and a frequency of 0.2 Hz. Sessions were continued once a week for 2 months. The 9 control patients showed no changes of symptoms between the initial evaluation and that after 2 months of sham rTMS. In contrast, all 9 patients receiving rTMS showed a significant decrease of the modified H&Y and UPDRS scores after 2 months, while the Schwab and England ADL Scale scores increased significantly. In the second CSF sample from patients receiving rTMS, HVA showed a significant decrease These results suggest that rTMS is beneficial for the symptoms of Parkinson's disease and that it may act via inhibition of dopaminergic systems.

Intermittent theta-burst transcranial magnetic stimulation for treatment of Parkinson disease

1. 2. 3. 4. 5. 6. 7. 8. D.H. Benninger, MD, B.D. Berman, MD, E. Houdayer, PhD, N. Pal, D.A. Luckenbaugh, L. Schneider, S. Miranda, MD and M. Hallett, MD

+ Author Affiliations 1. From the Medical Neurology Branch (D.H.B., B.D.B., E.H., N.P., L.S., S.M., M.H.), National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Mental Health (NIMH) (D.A.L.), National Institutes of Health, Bethesda, MD; and Department of Neurology (D.H.B.), University Hospital of Basel, Basel, Switzerland. 1. Address correspondence and reprint requests to Dr. David H. Benninger, Department of Neurology, University Hospital of Basel, Petersgraben 4, 4051 Basel, Switzerland benningerd@uhbs.ch

Abstract
Objective: To investigate the safety and efficacy of intermittent theta-burst stimulation (iTBS) in the treatment of motor symptoms in Parkinson disease (PD). Background: Progression of PD is characterized by the emergence of motor deficits, which eventually respond less to dopaminergic therapy and pose a therapeutic challenge. Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in improving gait, a major cause of disability, and may provide a therapeutic alternative. iTBS is a novel type of rTMS that may be more efficacious than conventional rTMS. Methods: In this randomized, double-blind, sham-controlled study, we investigated safety and efficacy of iTBS of the motor and dorsolateral prefrontal cortices in 8 sessions over 2 weeks (evidence Class I). Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia, Unified Parkinson's Disease Rating Scale (UPDRS), and additional clinical, neuropsychological, and neurophysiologic measures. Results: We investigated 26 patients with mild to moderate PD: 13 received iTBS and 13 sham stimulation. We found beneficial effects of iTBS on mood, but no improvement of gait, bradykinesia, UPDRS, and other measures. EEG/EMG monitoring recorded no pathologic increase of cortical excitability or epileptic activity. Few reported discomfort or pain and one experienced tinnitus during real stimulation. Conclusion: iTBS of the motor and prefrontal cortices appears safe and improves mood, but failed to improve motor performance and functional status in PD. Classification of evidence: This study provides Class I evidence that iTBS was not effective for gait, upper extremity bradykinesia, or other motor symptoms in PD.

The Use of Slow-Frequency Prefrontal Repetitive Transcranial Magnetic Stimulation in Refractory Neuropathic Pain
Sampson, Shirlene M. MD, MS; Kung, Simon MD; McAlpine, Donald E. MD; Sandroni, Paola MD, PhD

Abstract Objective: A number of antidepressant medications, as well as electroconvulsive therapy, have been shown to reduce chronic pain. Slow-frequency repetitive transcranial magnetic stimulation (rTMS) applied to the right dorsolateral prefrontal cortex has also been shown to have an antidepressant effect. Given the high degree of suffering experienced by subjects with chronic neuropathic pain and the treatment resistance noted in this population, the use of slow-frequency rTMS as adjuvant therapy may be of significant clinical benefit. Methods: Fifteen sessions of 1-Hz rTMS (1600 stimulations/session) were applied to the right dorsolateral prefrontal cortex as adjuvant treatment in 9 subjects with refractory neuropathic pain over 3 weeks. Pain and depression ratings were performed at baseline, weekly during rTMS treatment, and monthly for up to 3 months after treatment. Results: Five males and 4 females participated, and all had longstanding refractory neuropathic pain (range, 1-19 years), with an average baseline pain rating of 7.3 and no depression (Hamilton Rating Scale for Depression average, 3.6; range, 0-8). Three subjects had a greater than 50% decline in pain ratings by the completion of rTMS treatments, and 1 subject responded more slowly with greater than 50% improvement in pain by the end of the 3-month follow-up. An improvement in pain ratings was noted in responders within the first week. Conclusions: Although these are preliminary findings in an open treatment trial, the subjects in this trial are among the least likely to have a placebo response. Given that rTMS is a welltolerated and noninvasive intervention, any sustained improvement in neuropathic pain with rTMS is encouraging.

BAB 1 Neural Correlates of the Antinociceptive Effects of Repetitive

Transcranial Magnetic Stimulation on Central Pain After Stroke

1. Suk Hoon Ohn 1. Won Hyuk Chang 1. Chang-hyun Park 1. Sung Tae Kim 1. Jung Il Lee 1. Alvaro Pascual-Leone 1. Yun-Hee Kim, M.D., Ph.D. yunkim@skku.edu

Abstract
Background. Repetitive transcranial magnetic stimulation (rTMS) modulates central neuropathic pain in some patients after stroke, but the mechanisms of action are uncertain. Objective. The authors used diffusion tensor imaging (DTI) and functional MRI (fMRI) to evaluate the integrity of the thalamocortical tract (TCT) and the activation pattern of the pain network in 22 patients with poststroke central pain. Methods. Each patient underwent daily 10-Hz rTMS sessions for 1000 pulses on 5 consecutive days over the hotspot for the first dorsal interosseus muscle. Pain severity was monitored using the Visual Analogue Scale (VAS). Mood was assessed by the Hamilton Depression Rating Scale. Results. Clinical data from all participants along with the DTI and fMRI findings from 10 patients were analyzed. VAS scores decreased significantly, if modestly, following administration of rTMS in 14 responders, which lasted for 2 weeks after the intervention. Regression analysis showed a significant correlation between less initial depression and higher antalgic effect of rTMS. Integrity of the superior TCT in the ipsilesional hemisphere showed significant correlation with change of VAS score after rTMS. fMRI showed significantly decreased activity in the secondary somatosensory cortex, insula, prefrontal cortex, and putamen in rTMS responders, whereas no change was noted in nonresponders. Conclusion. Mood may affect the modest antinociceptive effects of rTMS that we found, which may be mediated by the superior TCT through modulation of a distributed pain network.

A Randomized, Placebo-Controlled Trial of Repetitive Spinal Magnetic Stimulation in Lumbosacral Spondylotic Pain
1. 2. 3. 4. Yew L. Lo MD1,*, Stephanie Fook-Chong MSc2, Antonio P. Huerto MD3, Jane M. George MD3

Article first published online: 13 JUN 2011

Abstract
Objective. Lumbar spondylosis is a degenerative disorder of the spine, whereby pain is a prominent feature that poses therapeutic challenges even after surgical intervention. There are no randomized, placebo-controlled studies utilizing repetitive spinal magnetic stimulation (SMS) in pain associated with lumbar spondylosis. In this study, we utilize SMS technique for patients with this condition in a pilot clinical trial. Methods. We randomized 20 patients into SMS treatment or placebo arms. All patients must have clinical and radiological evidence of lumbar spondylosis. Patients should present with pain in the lumbar region, localized or radiating down the lower limbs in a radicular distribution. SMS was delivered with a Medtronic R30 repetitive magnetic stimulator (Medtronic Corporation, Skovlunde, Denmark) connected to a C-B60 figure of eight coil capable of delivering a maximum output of 2 Tesla per pulse. The coil measured 90 mm in each wing and was centered over the surface landmark corresponding to the cauda equina region. The coil was placed flat over the back with the handle pointing cranially. Each patient on active treatment received 200 trains of five pulses delivered at 10 Hz, at an interval of 5 seconds between each train. Sham SMS was delivered with the coil angled vertically and one of the wing edges in contact with the stimulation point. Results. All patients tolerated the procedure well and no side effects of SMS were reported. In the treatment arm, SMS had resulted in significant pain reduction immediately and at Day 4 after treatment (P < 0.05). In the placebo arm, however, no significant pain reduction was seen immediately and at Day 4 after SMS. SMS in the treatment arm had resulted in mean pain reduction of 62.3% postprocedure and 17.4% at Day 4. The placebo arm only achieved pain reduction of 6.1% postprocedure and 4.5% at Day 4. Discussion. This is the first study to show that a single session of SMS resulted in significant improvement of pain associated with lumbar spondylosis in a randomized, doubleblind, placebo-controlled setting. The novel findings support the potential of this technique for future studies pertaining to neuropathic pain.

Comparison of coil designs for peripheral magnetic muscle stimulation

S M Goetz1, H-G Herzog1, N Gattinger2 and B Gleich2 Show affiliations

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Abstract References

The recent application of magnetic stimulation in rehabilitation is often said to solve key drawbacks of the established electrical method. Magnetic fields cause less pain, allow principally a better penetration of inhomogeneous biologic tissue and do not require skin contact. However, in most studies the evoked muscle force has been disappointing. In this paper, a comparison of a classical round circular geometry, a commercial muscle-stimulation coil and a novel design is presented, with special emphasis on the physical field properties. These systems show markedly different force responses for the same magnetic energy and highlight the enormous potential of different coil geometries. The new design resulted in a slope of the force recruiting curve being more than two and a half times higher than the other coils. The data were analyzed with respect to the underlying physical causes and field conditions. After a parameter-extraction approach, the results for the three coils span a twodimensional space with clearly distinguishable degrees of freedom, which can be manipulated nearly separately and reflect the two main features of a field; the peak amplitude and its decay with the distance.

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