Motor cortex stimulation for ALS: a double blind placebo-controlled study. The effect of repetitive transcranial magnetic stimulation on motor performance, fatigue and quality of life in amyotrophic lateral sclerosis. Repetitive transcranial magnetic stimulation for ALS. A preliminary controlled study. Low-frequency rTMS promotes use-dependent motor plasticity in chronic stroke: a randomized trial. A sham-controlled trial of a 5-day course of repetitive transcranial magnetic stimulation of the unaffected hemisphere in stroke patients. Effects of treatment intensity in upper limb robot-assisted therapy for chronic stroke: a pilot randomized controlled trial. A sham stimulation-controlled trial of rTMS of the unaffected hemisphere in stroke patients. A randomised controlled trial: outcomes of bladder rehabilitation in persons with multiple sclerosis. Long-term effect of repetitive transcranial magnetic stimulation on motor function recovery after acute ischemic stroke.
Preliminary data suggest that repetitive transcranial magnetic stimulation (rTMS) of the brain may produce a modest slowing of disease progression in amyotrophic lateral sclerosis (ALS). The present study was designed to test the hypothesis that rTMS given as continuous theta burst stimulation (cTBS), repeated monthly for one year, would affect ALS progression. We performed a double blind, placebo-controlled trial. Twenty patients with ALS were randomly allocated to blinded real or placebo stimulation. cTBS of the motor cortex was performed for five consecutive days every month for one year. Primary outcome was the rate of decline as evaluated with the revised ALS functional rating scale (ALSFRS-R). Treatment was well tolerated. There was no significant difference in the ALSFRS-R score deterioration between patients treated with real or placebo stimulation. ALSFRS-R mean scores declined from 32.0 (SD 7.1) at study entry to 23.1 (SD 6.3) at 12 months in patients receiving real cTBS and from 31.3 (SD 6.9) to 21.2 (SD 6.0) in those receiving placebo stimulation. Although cTBS proved a safe procedure, on the basis of the present findings a larger randomized confirmatory trial seems unjustified in ALS patients, at least in advanced stage of the disease. The treatment of amyotrophic lateral sclerosis (ALS) is still disappointing. Repetitive transcranial magnetic stimulation (rTMS) has been suggested to modify the rate of disease progression in ALS.
                In a pilot controlled study, we tested the effect of 5-Hz rTMS on motor performance, fatigue and quality of life (QoL) in ALS.
                Ten ALS patients underwent a two-week period of daily active or sham 5-Hz rTMS. Outcome measures were assessed with functional, fatigue and QoL scales. Muscle strength was evaluated with the MRC scale and measured with isometric and isokinetic dynamometer.
                Significant difference at the end of rTMS treatment was found for QoL, maximum voluntary isometric contraction and isokinetic average power when comparing active vs sham treatment. These changes were transitory and outcome measures were not significant two weeks after discontinuation of rTMS.
                Though preliminary, our results suggest that 5-Hz rTMS may improve motor function and QoL in ALS. The present data indicate the need of a double-blind therapeutic trial of rTMS in ALS. Repetitive transcranial magnetic stimulation (rTMS) of brain can modulate cortical neurotransmission, a novel paradigm of repetitive stimulation termed continuous theta-burst stimulation (cTBS) produces a pronounced and prolonged suppression of motor cortex excitability. The aim of this preliminary study was to investigate whether cTBS of motor cortex could have any beneficial effect in patients with amyotrophic lateral sclerosis (ALS). We performed a double-blind, placebo-controlled trial. Twenty patients with definite ALS were randomly allocated to blinded active or placebo stimulation. Repetitive stimulation of the motor cortex was performed for five consecutive days every month for six consecutive months. The primary outcome was the rate of decline as evaluated with the ALS functional rating scale. The treatment was well tolerated by the patients. Fifteen patients (seven active and eight sham) completed the study and were included in the 6-months analysis. Both active and sham patients deteriorated during treatment, however, active patients showed a modest but significant slowing of the deterioration rate. Though we cannot be sure whether the effects observed can be attributed to cTBS, because of the restricted number of patients studied, further investigation on a larger group of ALS patients is warranted. The results of the pilot study might open up a new therapeutic perspective in ALS based on neuromodulation. 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. 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. Robot-assisted therapy (RT) is a current promising intervention in stroke rehabilitation, but more research is warranted for examining its efficacy and the dose-benefit relation. The authors investigated the effects of higher intensity versus lower intensity RT on movements of forearm pronation-supination and wrist flexion-extension relative to conventional rehabilitation (CR) in patients poststroke for a mean of 21 months.
                In this pilot study, 18 patients with initial mean Fugl-Meyer Assessment (FMA) of 37 to 44 for the upper extremity were randomized to higher intensity RT, lower intensity RT, or CR intervention for 4 weeks. The dose of the higher intensity RT was twice the number of repetitions in the lower intensity RT. Outcome measures at pretreatment and posttreatment were administered to patients to evaluate beneficial and adverse effects of interventions. Primary outcomes were the FMA and Medical Research Council scale.
                There were significant differences in motor function (P = .04) and daily performance (P = .03) among the 3 groups. The higher intensity RT group showed better improvement in motor function, muscle strength, performance of daily activities, and bimanual ability than the other 2 groups. The intensive RT intervention did not induce higher levels of an oxidative DNA biomarker.
                Higher intensity of RT that assists forearm and wrist movements may lead to greater improvement in motor ability and functional performance in stroke patients. A sample size of only 20 to 25 in each arm of a larger randomized controlled trial is needed to confirm the findings for similar subjects. 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. A stratified, randomised, waitlist controlled study over 12 months assessed the effectiveness of a 6 week bladder rehabilitation programme in persons with multiple sclerosis (pwMS) in an Australian community cohort.
                Patients with definite MS and bladder issues (n=74) recruited from a tertiary hospital database were randomised to a treatment group (n=40) for an individualised bladder rehabilitation programme or to a control waitlist group (n=34). The Urogenital Distress Inventory (UDI6), Neurological Disability Scale (NDS) and the American Urological Association Symptom Index (AUA) assessed bladder impairment and 'activity limitation'; a single Quality of life (QoL) item in the AUA and the Incontinence Impact Questionnaire (IIQ7) measured restriction in 'participation'. Primary outcome measures were assessed at baseline and at 12 months.
                Analysis of per protocol data from 58 patients (treatment n=24, control n=34) showed reduced disability in the treatment group, with significant differences (p<0.001) and large effect sizes (>0.5) in post-treatment UDI6, NDS, AUA total, AUA QoL and IIQ7 scores for the two groups. The treatment group compared with the control group showed improvement: 78% versus 27% for UDI6 and 59% versus 17% improved for IIQ7. More patients in the control group deteriorated over the study period on the UDI6 (30% vs 0%; p<0.001) and IIQ7 (39 vs 0%; p=0.001).
                A multifaceted, individualised bladder rehabilitation programme reduces disability and improves QoL in pwMS compared with no intervention after 12 months of follow-up. Information on specific interventions in different bladder types in MS and the impact on QoL need further evaluation. Australian Clinical trials Registry ACTRNO12605000676617. 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.
There is currently insufficient evidence to draw conclusions about the efficacy and safety of rTMS in the treatment of ALS. Further studies may be helpful if their potential benefit is weighed against the impact of participation in a randomised controlled trial on people with ALS.