Long-term effect of repetitive transcranial magnetic stimulation on motor function recovery after acute ischemic stroke. A sham stimulation-controlled trial of rTMS of the unaffected hemisphere in stroke patients. [Effect of transcranial magnetic stimulation on rehabilitation of motor function in patients with cerebral infarction]. A sham-controlled trial of a 5-day course of repetitive transcranial magnetic stimulation of the unaffected hemisphere in stroke patients. Transcranial magnetic stimulation and muscle contraction to enhance stroke recovery: a randomized proof-of-principle and feasibility investigation. Repetitive transcranial magnetic stimulation as treatment of poststroke depression: a preliminary study. rTMS combined with task-oriented training to improve symmetry of interhemispheric corticomotor excitability and gait performance after stroke: a randomized trial. Inhibition of the unaffected motor cortex by 1 Hz repetitive transcranical magnetic stimulation enhances motor performance and training effect of the paretic hand in patients with chronic stroke. Low-frequency rTMS promotes use-dependent motor plasticity in chronic stroke: a randomized trial. Therapeutic trial of repetitive transcranial magnetic stimulation after acute ischemic stroke. Repetitive transcranial magnetic stimulation as an adjunct to constraint-induced therapy: an exploratory randomized controlled trial. θ-burst stimulation of the left hemisphere accelerates recovery of hemispatial neglect. Role of 1 and 3 Hz repetitive transcranial magnetic stimulation on motor function recovery after acute ischaemic stroke. Effects of repetitive transcranial magnetic stimulation in aphasic stroke: a randomized controlled pilot study. Contralesional repetitive transcranial magnetic stimulation for chronic hemiparesis in subcortical paediatric stroke: a randomised trial. Improved language performance subsequent to low-frequency rTMS in patients with chronic non-fluent aphasia post-stroke. Improvement of dexterity by single session low-frequency repetitive transcranial magnetic stimulation over the contralesional motor cortex in acute stroke: a double-blind placebo-controlled crossover trial.
Although there is evidence for short term benefits of rTMS in stroke, longer term effects have not been reported. The aim of the study was to evaluate the effect of two different frequencies of rTMS on motor recovery and on cortical excitability up to 1 year post-treatment.
                Forty-eight patients with acute ischemic stroke were randomly classified into three groups. The first two groups received real rTMS over motor cortex (3 and 10 Hz respectively) of the affected hemisphere and the third group received sham stimulation of the same site, daily for five consecutive days. Disability was assessed before, after fifth sessions, and then after 1, 2, 3 and 12 months. Cortical excitability was assessed for both hemispheres before and after the second and fifth sessions.
                A significant 'rTMS x time' interaction was obtained indicating that real and sham rTMS had different effects on rating scales. This was because real rTMS produced greater improvement than sham that was evident even at one year follow-up. These improvements were associated with changes in cortical excitability over the period of treatment.
                These results confirm that real rTMS over motor cortex can enhance and maintain recovery and may be a useful add on therapy in treatment of acute stroke patients. The authors investigated the use of slow-frequency repetitive transcranial magnetic stimulation (rTMS) to the unaffected hemisphere to decrease interhemispheric inhibition of the lesioned hemisphere and improve motor function in patients within 12 months of a stroke. Patients showed a significant decrease in simple and choice reaction time and improved performance of the Purdue Pegboard test with their affected hand after rTMS of the motor cortex in the intact hemisphere as compared with sham rTMS. To study the effect of transcranial magnetic stimulation (TMS) on the rehabilitation of motor function in patients with cerebral infarction.
                Two hundred twenty and three patients with the initial attack of cerebral infarction were divided into three groups. (1) One hundred twenty and three patients were randomly further divided into rehabilitation subgroup (n = 63, aged 64.0 +/- 7.9, treated with TMS beginning from the 6 approximately 10 th day after onset) and control subgroup (n = 60, aged 63.5 +/- 7.9). (2) Sixty patients were divided into three subgroups according to the age: 35 approximately 55 (n = 11), 56 approximately 75 (n = 20), and over 76 (n = 30). (3) Forty patients aged 56 approximately 75 were further divided into two subgroups according to the timing of beginning of TMS: subgroup with TMS beginning within 3 months after the initial attack (n = 20) and subgroup with TMS beginning 3 months after the initial attack (n = 20). Except for TMS, the basic treatment was the same for all of the patients. TMS was given once a day for 14 days. Fugl-Meyer score, Barthel index, and central spinal cord motor conduction time (CMCT) were measured twice: just before treatment and after the 14th treatment. A difference less than 20 ms between CMCT values measured before and after TMS and failure to induce CMCT both before and after TMS were regarded as ineffective hess, and a difference more than 20 ms between CMCT values measured before and after TMS and a change from failure to induce CMCT were regarded as effective hess.
                The effective rate was 90.5% in the rehabilitation subgroup and 68.3% in the control group (P < 0.05). The Fugl-Meyer scores were 36.3 +/- 15.8 and 33.7 +/- 13.7 in the rehabilitation subgroup and control subgroup before treatment respectively (P > 0.05), and were 51.7 +/- 15.7 and 40.0 +/- 13.9 after treatment respectively (P < 0.01). The Barthel index were 39.6 +/- 15.8 and 40.0 +/- 14.9 in the two subgroups before treatment respectively (P > 0.05) and were 50.5 +/- 15.7 and 43.9 +/- 15.3 after treatment respectively (P < 0.05). The Fugl-Meyer scores before and after TMS were 35.8 +/- 11.3 and 61.6 +/- 18.6 in the subgroup aged 35 approximately 55 (P < 0.01), 33.5 +/- 14.0 and 49.2 +/- 16.0 in the subgroup aged 56 approximately 75 (P < 0.001), and 32.1 +/- 10.7 and 37.6 +/- 11.3 in the subgroup aged over 75 (P > 0.05). The Fugl-Meyer scores were 41.2 +/- 15.7 and 59.0 +/- 22.8 before and after TCM respectively in the subgroup with early TMS treatment (P < 0.01), and were 34.3 +/- 13.5 and 45.4 +/- 14.8 respectively in the subgroup with TMS beginning 3 months after the onset (P < 0.05).
                TMS is effective on the rehabilitation of motor function in patients with cerebral infarction. The effectiveness of TMS treatment depends on the age of the patients and timing of beginning treatment. It has been recently shown that a single session of repetitive transcranial magnetic stimulation (rTMS) of the unaffected hemisphere can improve motor function in stroke patients; however, this improvement is short-lasting. We therefore conducted a randomized, sham-controlled, phase II trial to evaluate whether five sessions of low-frequency rTMS can increase the magnitude and duration of these effects and whether this approach is safe.
                Fifteen patients with chronic stroke were randomized to receive active or sham rTMS of the unaffected hemisphere. A blinded rater assessed motor function and corticospinal excitability at baseline, during and after 2 weeks of treatment. Safety was assessed using a neuropsychologic battery and electroencephalogram.
                Active rTMS resulted in a significant improvement of the motor function performance in the affected hand that lasted for 2 weeks. These effects were not observed in the sham rTMS group (affected and unaffected hand) and in the unaffected hand in the active rTMS group. Corticospinal excitability decreased in the stimulated, unaffected hemisphere and increased in the affected hemisphere. There was a significant correlation between motor function improvement and corticospinal excitability change in the affected hemisphere. Cognitive performance and electroencephalogram were not changed significantly throughout the trial in both groups of treatment.
                These results support and extend the findings of previous studies on rTMS in stroke patients because five consecutive sessions of rTMS increased the magnitude and duration of the motor effects. Furthermore, this increased dose of rTMS is not associated with cognitive adverse effects and/or epileptogenic activity. To explore the efficacy of repetitive transcranial magnetic stimulation (rTMS) and voluntary muscle contraction (VMC) to improve corticospinal transmission, muscle function, and purposeful movement early after stroke.
                Factorial 2 x 2 randomized single-blind trial.
                n = 27, mean age 75 years, mean 27 days after middle cerebral artery infarct (24 subjects completed outcome measures).
                after baseline measurement (day 1), subjects were randomized to 1 of 4 groups. Treatment was given for the next 8 working days, and outcome was measured on day 10.
                (a) Real-rTMS + RealVMC, (b) Real-rTMS + PlaceboVMC, (c) Placebo-rTMS + RealVMC, and (d) Placebo-rTMS + PlaceboVMC. Real-rTMS consisted of 200 1-Hz stimuli at 120% motor threshold in 5 blocks of 40 separated by 3 minutes delivered to the lesioned hemisphere. Placebo-rTMS used a dummy coil. In RealVMC, the paretic elbow was repeatedly flexed/extended for 5 minutes. In PlaceboVMC, subjects viewed pairs of drawings of upper limbs and reported their likeness.
                frequency of motor-evoked potentials in biceps and triceps, muscle function (torque about elbow), and purposeful movement (Action Research Arm Test).
                group mean changes (outcome - baseline) were compared.
                In the Real-rTMS + RealVMC group, motor-evoked potential frequency increased 14% for biceps and 20% for triceps, whereas in the Placebo-rTMS + PlaceboVMC group, it decreased 12% for biceps and 6% for triceps. For other groups, there were changes of intermediate values. No meaningful differences were found for secondary outcomes.
                A positive trend for motor-evoked potential frequency was found for Real-rTMS + RealVMC, whereas a negative trend for motor-evoked potential frequency was found for Placebo-rTMS + PlaceboVMC. Depression has a significant impact on poststroke recovery and mortality. There are a proportion of patients with poststroke depression (PSD) who do not respond to antidepressants. Repetitive Transcranial Magnetic Stimulation (rTMS) might be a safe and effective alternative in these refractory cases.
                We conducted a randomized, parallel, double-blind study of active versus sham left prefrontal rTMS in patients with refractory PSD. After discontinuing antidepressants, patients were randomly assigned to receive 10 sessions of active (10 Hz, 110% of the motor threshold, 20 trains of 5 seconds duration) or sham left prefrontal rTMS. Efficacy measures included HAM-D scores, response and remission rates. Patients completed a neuropsychological battery at baseline and after completing the protocol.
                When compared with sham stimulation, 10 sessions of active rTMS of the left dorsolateral prefrontal cortex were associated with a significant reduction of depressive symptoms. This reduction was not influenced by patient's age, type or location of stroke, volume of left frontal leukoaraiosis or by the distance of the stimulating coil to the prefrontal cortex. However, there was a significant positive correlation between the percentage of reduction of Ham-D scores and frontal gray and white matter volumes. There were no significant changes in cognitive functioning between the active and the sham stimulation groups. In addition, there were few and mild adverse effects that were equally distributed among groups.
                Taken together, these preliminary findings suggest that rTMS may be an effective and safe treatment alternative for patients with refractory depression and stroke. The model of interhemispheric competition after stroke has been established for the upper but not for the lower extremity. Repetitive transcranial magnetic stimulation (rTMS) of the brain has been shown to modulate cortical excitability.
                The purpose of this study was to investigate the effects of rTMS followed by task-oriented training on cortical excitability and walking performance in individuals with chronic stroke.
                A total of 24 patients with average Fugl-Meyer lower limb scores of 17.88 ± 5.27 and average walking speeds of 63.81 ± 18.25 cm/s were randomized into an experimental group and a control group. Participants received rTMS (experimental group) or sham rTMS (control group) followed by task-oriented training (30 minutes) for 10 sessions over 2 weeks. Repetitive TMS was applied at a 1-Hz frequency over the leg area of the motor cortex of the unaffected hemisphere for 10 minutes. Outcomes, including motor-evoked potential (MEP), lower-extremity Fugl-Meyer score, and gait performance, were measured before and after training.
                Decreased interhemispheric asymmetry of the amplitude of the MEP was noted after rTMS and task-oriented training. Improvement in spatial asymmetry of gait was comparable with increased symmetry in interhemispheric excitability. Motor control and walking ability were also significantly improved after rTMS and task-oriented training.
                rTMS enhances the effect of task-oriented training in those with chronic stroke, especially by increasing gait spatial symmetry and corticomotor excitability symmetry. Recent reports demonstrated that low-frequency repetitive transcranial magnetic stimulation (rTMS) over the unaffected hemisphere improved the affected hand function in chronic stroke patients. We investigated whether 1 Hz rTMS improved the motor learning of the affected hand in patients after stroke.
                A double-blind study.
                Twenty patients with chronic subcortical stroke.
                The patients were randomly assigned to receive either a sub-threshold rTMS over the unaffected hemisphere (1 Hz, 25 minutes) or sham stimulation, and all patients performed a pinching task after stimulation. We evaluated the motor function of the affected hand and the excitatory and inhibitory function of the affected motor cortex by transcranial magnetic stimulation.
                Compared with sham stimulation, rTMS induced an increase in the excitability of the affected motor cortex(p < 0.001) and an improvement in acceleration of the affected hand (p = 0.006). Moreover, the effect of motor training on pinch force was enhanced by rTMS (p < 0.001). These improvement in the motor function lasted for one week after rTMS and motor training (p < 0.001).Conclusion: rTMS improved the motor learning of the affected hand in patients after stroke; thus, it can apply as anew rehabilitation strategy for patients after stroke. To investigate the long-term behavioral and neurophysiologic effects of combined time-locked repetitive transcranial magnetic stimulation (rTMS) and physical therapy (PT) intervention in chronic stroke patients with mild motor disabilities.
                Thirty patients were enrolled in a double-blind, randomized, single-center clinical trial. Patients received 10 daily sessions of 1 Hz rTMS over the intact motor cortex. In different groups, stimulation was either real (rTMS(R)) or sham (rTMS(S)) and was administered either immediately before or after PT. Outcome measures included dexterity, force, interhemispheric inhibition, and corticospinal excitability and were assessed for 3 months after the end of treatment.
                Treatment induced cumulative rebalance of excitability in the 2 hemispheres and a reduction of interhemispheric inhibition in the rTMS(R) groups. Use-dependent improvements were detected in all groups. Improvements in trained abilities were small and transitory in rTMS(S) patients. Greater behavioral and neurophysiologic outcomes were found after rTMS(R), with the group receiving rTMS(R) before PT (rTMS(R)-PT) showing robust and stable improvements and the other group (PT-rTMS(R)) showing a slight improvement decline over time.
                Our findings indicate that priming PT with inhibitory rTMS is optimal to boost use-dependent plasticity and rebalance motor excitability and suggest that time-locked rTMS is a valid and promising approach for chronic stroke patients with mild motor impairment. Classification of evidence: This interventional study provides Class I evidence that time-locked rTMS before or after physical therapy improves measures of dexterity and force in the affected limb in patients with chronic deficits more than 6 months poststroke. Repetitive transcranial magnetic stimulation (rTMS) or sham stimulation was given over the motor cortex daily for 10 days to two randomly assigned groups of 26 patients with acute ischemic stroke. Patients otherwise continued their normal treatment. Disability scales measured before rTMS, at the end of the last rTMS session, and 10 days later showed that real rTMS improved patients' scores more than sham. To test the potential adjuvant effect of repetitive transcranial magnetic stimulation (rTMS) on motor learning in a group of stroke survivors undergoing constraint-induced therapy (CIT) for upper-limb hemiparesis.
                This was a prospective randomized, double-blind, sham-controlled, parallel group study. Nineteen individuals, one or more years poststroke, were randomized to either a rTMS + CIT (n = 9) or a sham rTMS + CIT (n = 10) group and participated in the 2-wk intervention.
                Regardless of group assignment, participants demonstrated significant gains on the primary outcome measures: the Wolf Motor Function Test (WMFT) and the Motor Activity Log (MAL)--Amount of Use, and on secondary outcome measures including the Box and Block Test (BBT) and the MAL--How Well. Participants receiving rTMS failed to show differential improvement on either primary outcome measure.
                Although this study provided further evidence that even relatively brief sessions of CIT can have a substantial effect, it provided no support for adjuvant use of rTMS. Cortico-cortical circuits originating from the posterior parietal cortex (PPC) of the intact left hemisphere (LH) may become hyperexcitable in patients with hemispatial neglect due to a right hemispheric (RH) stroke.
                In the current randomized, double-blind, sham-controlled study, we investigated safety and efficacy of continuous theta-burst stimulation (cTBS) in 10 sessions over 2 weeks applied over the intact PPC of the LH in subacute ischemic stroke patients. Severity of neglect was assessed through the standardized Behavioral Inattention Test (BIT). We also measured, by means of bifocal transcranial magnetic stimulation (TMS), how cTBS modified the excitability of the parieto-frontal functional connections in the intact LH.
                We found that 2 weeks of cTBS, but not sham cTBS, were effective in improving neglect symptoms as measured by BIT score. BIT scores improved by 16.3% after 2 weeks of cTBS and 22.6% at 1 month follow-up. We also found that hyperexcitability of LH parieto-frontal circuits was reduced following treatment with real but not sham cTBS.
                These findings suggest that a 2-week course of cTBS over the LH PPC may be a potential effective strategy in accelerating recovery from visuospatial neglect in subacute stroke patients, possibly counteracting the hyperexcitability of LH parieto-frontal circuits. Classification of evidence: This study provides Class III evidence that left posterior parietal cortex theta-burst stimulation improves hemispatial neglect for up to 2 weeks after treatment. The purpose of this study was to compare the long-term effect of five daily sessions of 1 vs. 3 Hz repetitive transcranial magnetic stimulation (rTMS) on motor recovery in acute stroke.
                A total of 36 patients with acute ischaemic stroke participated in the study. The patients were randomly assigned into one of three groups; the first and second groups received real rTMS; 1 and 3 Hz and third group received sham stimulation, daily for 5 days. Motor disability was assessed before and after the last session, and then after first, second and third month. Cortical excitability was assessed before and after the second and fifth session. The outcome measure was clinical disability at 3 months post-rTMS.
                No significant differences were found in basal rating scales between the three groups. At the 3-month time point, both of the real rTMS groups had improved significantly more in different rating scales than the sham group; in addition, the 1 Hz group performed better than the 3 Hz group. Measures of cortical excitability immediately after the last session showed that the 1 Hz group had reduced excitability of the non-stroke hemisphere and increased excitability of the stroke hemisphere, whereas the 3 Hz group only showed increased excitability of the stroke hemisphere.
                These results confirm that five daily sessions of rTMS over motor cortex using either 1 Hz over the unaffected hemisphere or 3 Hz over the affected hemisphere can enhance recovery. At 3 months, the improvement was more pronounced in 1 Hz group. Although functional imaging studies suggest that recruitment of contralesional areas hinders optimal functional reorganization in patients with aphasic stroke, only limited evidence is available on the efficacy of noninvasive brain stimulation such as repetitive transcranial magnetic stimulation aimed at suppression of contralateral overactivation.
                In this randomized, controlled, blinded pilot study, the effect of 1-Hz repetitive transcranial magnetic stimulation over right-hemispheric Broca homolog in subjects with poststroke aphasia in the subacute stage was examined. According to their group allocation, patients received, in addition to conventional speech and language therapy, multiple sessions of repetitive transcranial magnetic stimulation either over the right-hemispheric inferior frontal gyrus (intervention group) or over the vertex (control group). The primary outcome parameter was the change in laterality indices as quantified by activation positron emission tomography before and after the 2-week intervention period. The clinical efficacy was evaluated with the Aachen Aphasia Test.
                At baseline, no group differences were discovered for age, laterality indices, or mean Aachen Aphasia Test scores. Four patients were lost to follow-up, but none due to side effects of the transcranial magnetic stimulation. Positron emission tomography revealed an activation shift toward the right hemisphere in the control group (P=0.0165), which was absent in the intervention group. Furthermore, the latter improved significantly clinically by a mean of 19.8 points in the Aachen Aphasia Test total score (P=0.002), whereas the control group did not. There was however no clear linear relationship between the extent of laterality shift and clinical improvement (r=0.193, P=nonsignificant).
                Repetitive transcranial magnetic stimulation might be an effective, safe, and feasible complementary therapy for poststroke aphasia. Arterial ischaemic stroke (AIS) can cause disabling hemiparesis in children. We aimed to test whether contralesional, inhibitory repetitive transcranial magnetic stimulation (rTMS) could affect interhemispheric inhibition to improve hand function in chronic subcortical paediatric AIS.
                Patients were eligible for this parallel, randomised trial if they were in the SickKids Children's Stroke Program and had subcortical AIS more than 2 years previously, had transcallosal sparing, were more than 7 years of age, had hand motor impairment, had no seizures or dyskinesia, and were taking no drugs that alter cortical excitability. Patients were paired for age and weakness and were randomised within each pair to sham treatment or inhibitory, low-frequency rTMS over contralesional motor cortex (20 min, 1200 stimuli) once per day for 8 days. An occupational therapist did standardised tests of hand function at days 1 (baseline), 5, 10, and 17 (1 week post-treatment), and the primary outcomes were changes in grip strength and the Melbourne assessment of upper extremity function (MAUEF) between baseline and day 10. Patients, parents, and occupational therapists were blinded to treatment allocation. Analysis was per protocol.
                Ten patients with paediatric stroke were enrolled (median age 13.25 [IQR 10.08-16.78] years, mean time post-stroke 6.33 [SD 3.56] years): four with mild weakness, two with moderate weakness, and four with severe weakness. A repeated-measures ANOVA showed a significant interaction between time and the effect of treatment on grip strength (p=0.03). At day 10, grip strength was 2.28 (SD 1.01) kg greater than baseline in the rTMS group and 2.92 (1.20) kg less than baseline in the sham group (p=0.009). Benefits in mean grip strength persisted at day 17 (2.63 [0.56] kg greater than baseline with rTMS and 1.00 [0.70] kg less than baseline with sham treatment; p=0.01). Day 10 MAUEF score improved by more in the rTMS group than in the sham group (7.25 [3.8] vs 0.79 [1.3] points greater than baseline; p=0.002), but this benefit did not persist to day 17. Function of the unaffected hand remained stable. rTMS was well tolerated with no serious adverse events.
                Contralesional inhibitory rTMS was safe and feasible for patients with paediatric subcortical AIS, and seemed to improve hand function in patients with hemiparesis. Further studies are required to confirm the potential role of rTMS in paediatric neurorehabilitation.
                Canadian Stroke Consortium; Canadian Institutes of Health Research; American Academy of Neurology Foundation; Alberta Heritage Foundation for Medical Research. Low-frequency repetitive transcranial magnetic stimulation (rTMS) has emerged as a potential tool for neurorehabilitation and remediation of language in chronic non-fluent aphasia post-stroke. Inhibitory (1 Hz) rTMS has been applied to homologous language sites to facilitate behavioural language changes. Improvements in picture-naming performance and speech output over time have been reported.
                Low-frequency (1 Hz) rTMS was applied to six real stimulation and six sham placebo patients for 20 min per day, for 10 days, and behavioural language outcome measures were taken at baseline (pre-stimulation) and 2 months post-stimulation.
                The findings demonstrate treatment-related changes observed in the stimulation group when compared to the placebo control group at 2 months post-stimulation on naming performance as well as other aspects of expressive language and auditory comprehension.
                These findings provide considerable evidence to support the theory of rTMS modulating mechanisms of transcallosal disinhibition in the aphasic brain and highlight the potential clinical applications for language rehabilitation post-stroke.
                © 2010 The Author(s). European Journal of Neurology © 2010 EFNS. Increasing evidence suggests that the contralesional motor cortex (M1) inhibits the ipsilesional M1 in stroke patients. This inhibition could impair motor function of the affected hand. We investigated if inhibitory 1~Hz repetitive transcranial magnetic stimulation (rTMS) over the contralesional M1 improved motor performance of the affected hand in acute stroke.
                A double-blind study of real versus placebo rTMS was conducted. Twelve patients early after subcortical stroke (mean: 7 days) received 1200 stimuli of real and placebo rTMS in a crossover design. The sequence of stimulations was counterbalanced across subjects. Stimulus intensity was subthreshold (90% of motor threshold at rest). Motor function was tested by grip strength recordings and Nine Hole Peg Test (NHPT) executions before and after each rTMS session.
                Compared to sham stimulation, real rTMS improved NHPT results but not grip strength in the affected hand. No change of performance was observed for the unaffected hand. NHPT baseline repetitions in a subgroup of patients indicated stable motor performance prior to the rTMS sessions.
                The study suggests that therapeutic rTMS applications over the contralesional hemisphere are feasible in acute stroke patients and can transiently improve dexterity of the affected hand. RTMS may become an additional tool for early neurorehabilitation.