Repetitive transcranial magnetic stimulation (rTMS) technology, which is amongst the most used non-invasive brain stimulation techniques currently available, has developed rapidly from 2009 to 2018. However, reports on the trends of rTMS using bibliometric analysis are rare. The goal of the present bibliometric analysis is to analyze and visualize the trends of rTMS, including general (publication patterns) and emerging trends (research frontiers), over the last 10 years by using the visual analytic tool CiteSpace V. Publications related to rTMS from 2009 to 2018 were retrieved from the Web of Science (WoS) database, including 2,986 peer-reviewed articles/reviews. Active authors, journals, institutions, and countries were identified by WoS and visualized by CiteSpace V, which could also detect burst changes to identify emerging trends. GraphPad Prism 8 was used to analyze the time trend of annual publication outputs. The USA ranked first in this field. Pascual-Leone A (author A), Fitzgerald PB (author B), George MS (author C), Lefaucheur JP (author D), and Fregni F (author E) made great contributions to this field of study. The most prolific institution to publish rTMS-related publications in the last decade was the University of Toronto. The journal Brain Stimulation published most papers. Lefaucheur et al.’s paper in 2014, and the keyword “sham controlled trial” showed the strongest citation bursts by the end of 2018, which indicates increased attention to the underlying work, thereby indicating the research frontiers. This study reveals the publication patterns and emerging trends of rTMS based on the records published from 2009 to 2018. The insights obtained have reference values for the future research and application of rTMS.
This study conducts a bibliometric analysis of rTMS on the basis of records published from 2009 to 2018 to identify the publication patterns and emerging trends of this technique and gain new insights to guide future research and application.[…]
At Neuroelectrics, we believe in the advantages and effectiveness of transcranial electric stimulation (tES) in treating numerous brain diseases. Yet, despite the increasing number of tES publications per year, the lion’s share in the market of non-invasive brain stimulation technologies is still played by transcranial magnetic stimulation (TMS), likely because TMS received US-FDA approval in 2008 whereas tES has not yet.
Does this mean TMS is more effective? Well, it’s not quite fair to say so, considering TMS studies started at least 10 years earlier than those of tES. Therefore, there are several more clinical trials proving TMS efficacy.
However, the two techniques are close relatives: you can think of TMS as the elderly, stiff and sturdy brother, and tES as the younger, more flexible and easy-going one.
In this blogpost, we’ll go over the roots of their differences and see when and why you might prefer one over the other.
[E-fields patterns and biophysical substrates]
At a fundamental level, the two techniques rely on different physics and induce distinct patterns of electric fields (E-field) on the cortex, acting on a different neural substrate.
TMS is based on electromagnetic induction: a large magnetic coil is placed just a few centimetres above the scalp to stimulate over a specific cortical area. When the operator launches the electric pulse, vast amounts of current flows suddenly through the coil and creates a magnetic field around it, which varies rapidly in time. This changing magnetic field induces a very short (order of 1ms), highly localized (figure 1), super-threshold (order of 100V/m) E-field in the cortex. The E-field maximum is reached on the gyrus right under the coil, and the orientation is mostly parallel to the cortical surface.
The most sensitive cells to an E-field with such characteristics are interneurons and collaterals of pyramidal cells aligned tangentially to the cortical surface, which are automatically triggered to fire.
Instead, tES operates in the (quasi-)static regime, as only a small amount of direct current (DC) or low frequency alternating current (AC) is applied through electrodes placed directly on the scalp. The temporal resolution of the technique is low because the neuromodulatory effects begins a few seconds after the start of stimulation. Moreover, the E-field generated is much weaker (order of 0.1V/m) and less focalized (although the focality can be improved by using multichannel montages, it remains much lower than TMS E-field). Depending on the electrodes’ geometry, the maxima can occur on the gyri at the edges of the electrodes or between them. The overall orientation of the E-field is normal to the cortical surface, which indicates that tES probably influences layer V pyramidal neurons, as they are mostly perpendicular to the cortex.
Given the low, subthreshold intensity, the tES E-field cannot cause neural firing, but it is able to modulate the firing rate, facilitating or inhibiting the activation of pyramidal cells.
Other important differences concerning system setup.
TMS technology is more complex and cumbersome. The cost of the whole equipment is between 50-100k USD or Euros. This includes a wall-powered and heavy stimulator about the size of a fridge, a coil connected to the stimulator by a high-voltage cable, a mechanical arm to hold it in place, and a neuro-navigation system to accurately place the coil over the target brain region. The coil hangs suspended over the head of the patient, and since the strength of the effects depends on the coil-cortex distance, it’s crucial to keep it at the specific distance. For this, during the treatment session, the patient must sit still in a specially designed chair, with positioning frames around the chin and forehead.
On the contrary, tES is much cheaper and effortless: the cost is between an average of 6-30k USD/Euros, and the whole setup fits a shoe box. The stimulator can be as small as a mobile phone, light/portable, and almost always battery powered. The electrodes are directly in contact with the scalp, held in place by a rubber band or a neoprene cap. This way, the patient can move and even walk during the stimulation session.
Despite the underlying differences, TMS and tES are both quite versatile tools for treatment and research, and they offer similar options.
In research settings, you can leverage on TMS’ high spatial and temporal resolution to study how brain networks dynamically operate. In this context, TMS is usually performed online (during task performance) by applying one pulse at the onset of a stimulus (single-pulse TMS), or two pulses over separate regions which are interconnected (paired-pulses TMS). But tES too allows one to study the causal link between cortical areas. For instance, with tACS, one can simultaneously apply oscillatory currents over distinct regions at the same frequency but with different phases to promote or hamper the synchronization of functional networks.
Clinical applications of brain stimulation techniques instead tend to focus more on long-term effects, promoting network neuroplasticity that can outlast the period of stimulation.
In this case, TMS is usually ran in the repetitive mode (rTMS), which consists in multiple pulses within just microseconds. Frequency lower than 1Hz has been linked to long term depression (LTD), whereas frequency above 5Hz to long term potentiation (LTP). Similar outcomes can be achieved with tCS using either tDCS anodal or cathodal stimulation, which has been shown promoting and inhibiting synaptic activation, respectively.
The side effects of both techniques are quite moderate – with one important exception. While tES can induce only mild and temporary itching, tingling, and skin reddening when done properly, TMS might cause mild headaches, facial twitching, seizures in extreme cases.
For both TMS and tES, medical treatment must be performed mostly in clinical settings, which means you will have to find a clinician who provides these services in their clinic. However, one of the strengths of tES is the possibility to perform stimulation telemedically (under the remote guidance of a clinicians) via home-treatment. This is important as it will boost therapeutic effects for pathologies such as motor rehabilitation, depression, Alzheimer’s disease, etc in the comfort of one’s home. And it has been shown that the number of sessions modulates the length of the long-term plastic effects.
Interested in home-application of tCS? Check our home-kit here.
Polanía R, Nitsche M.A., Ruff C., Studying and modifying brain function with non-invasive brain stimulation, Nat. neurosci., 21:174–187 (2018)
Dayan E., Censor N., Buch E.R., Sandrini M, Cohen L.G., Noninvasive brain stimulation: from physiology to network dynamics and back, Nat. Neurosci., 16:838–844 (2013)
Salvador R., Wenger C., Miranda P.C. Investigating the cortical regions involved in MEP modulation in tDCS, Front. Cell. Neurosci. 9:405 (2015)
Acute brain ischemia causes changes in several neural networks and related cortico-subcortical excitability, both in the affected area and in the apparently spared contralateral hemisphere. The modulation of these processes through modern techniques of noninvasive brain stimulation, namely repetitive transcranial magnetic stimulation (rTMS), has been proposed as a viable intervention that could promote post-stroke clinical recovery and functional independence. This review provides a comprehensive summary of the current evidence from the literature on the efficacy of rTMS applied to different clinical and rehabilitative aspects of stroke patients. A total of 32 meta-analyses published until July 2019 were selected, focusing on the effects on motor function, manual dexterity, walking and balance, spasticity, dysphagia, aphasia, unilateral neglect, depression, and cognitive function after a stroke. Only conventional rTMS protocols were considered in this review, and meta-analyses focusing on theta burst stimulation only were excluded. Overall, both HF-rTMS and LF-rTMS have been shown to be safe and well-tolerated. In addition, the current literature converges on the positive effect of rTMS in the rehabilitation of all clinical manifestations of stroke, except for spasticity and cognitive impairment, where definitive evidence of efficacy cannot be drawn. However, routine use of a specific paradigm of stimulation cannot be recommended yet due to a significant level of heterogeneity of the studies in terms of protocols to be set and outcome measures that have to be used. Future studies need to preliminarily evaluate the most promising protocols before going on to multicenter studies with large cohorts of patients in order to achieve a definitive translation into daily clinical practice.
Stroke is a common acute neurovascular disorder that causes disabling long-term limitations to daily living activities. The most common consequence of a stroke is motor deficit of variable degree,1 although nonmotor symptoms are also relevant and often equally disabling.2 To date, to the best of the authors’ knowledge, there is no validated treatment that is able to restore the impaired functions by a complete recovery of the damaged tissue. Indeed, stroke management basically consists of reducing the initial ischemia in the penumbra, preventing future complications, and promoting a functional recovery using physiotherapy, speech therapy, occupational therapy, and other conventional treatments.3,4
Ischemic damage is associated with significant metabolic and electrophysiological changes in cells and neural networks involved in the affected area. From a pure electrophysiological perspective, however, beyond the affected area, there is a local shift in the balance between the inhibition and excitation of both the affected and contralateral hemisphere, consisting of increased excitability and disinhibition (reduced activity of the inhibitory circuits).3,5 In addition, subcortical areas and spinal regions may be altered.3,5 In particular, the role of the uninjured hemisphere seems to be of utmost significance in post-stroke clinical and functional recovery.
Different theoretical models have been proposed to explain the adaptive response of the brain to acute vascular damage. According to the vicariation model, the activity of the unaffected hemisphere contributes to the functional recovery after a stroke through the replacement of the lost functions of the affected areas. The interhemispheric competition model considers the presence of mutual inhibition between the hemispheres, and the damage caused by a stroke disrupts this balance, thus producing a reduced inhibition of the unaffected hemisphere by the affected side. This results in increased inhibition of the affected hemisphere by the unaffected side. More recently, a new model, called bimodal balance recovery, has been proposed.3,5 It introduces the concept of a structural reserve, which describes the extent to which the nondamaged neural pathways contribute to the clinical recovery. The structural reserve determines the prevalence of the interhemispheric imbalance over vicariation. When the structural reserve is high, the interhemispheric competition model can predict the recovery better than the vicariation model, and vice versa.3
Repetitive transcranial magnetic stimulation
One of the proposed interventions to improve stroke recovery, by the induction of neuromodulation phenomena, is based on methods of noninvasive brain stimulation. Among them, transcranial magnetic stimulation (TMS) is a feasible and painless neurophysiological technique widely used for diagnostic, prognostic, research, and, when applied repetitively, therapeutic purposes.6–9 By electromagnetic induction, TMS generates sub or suprathreshold currents in the human cortex in vivo and in real time.10,11
The most common stimulation site is the primary motor cortex (M1), that generates motor evoked potentials (MEPs) recorded from the contralateral muscles through surface electromyography electrodes.11 The intensity of TMS, measured as a percentage of the maximal output of the stimulator, is tailored to each patient based on the motor threshold (MT) of excitability. Resting MT (rMT) is found when the target muscle is at rest, it is defined as the minimal intensity of M1 stimulation required to elicit an electromyography response with a peak-to-peak amplitude > 50 µV in at least 5 out of 10 consecutive trials.11 Alternatively TMS MTAT 2.0 software (http://www.clinicalresearcher.org/software.htm) is a free tool for TMS researchers and practitioners. It provides four adaptive methods based on threshold-tracking algorithms with the parameter estimation by sequential testing, using the maximum-likelihood strategy for estimating MTs. Active MT (aMT) is obtained during a tonic contraction of the target muscle at approximately 20% of the maximal muscular strength.11
The rMT is considered a basic parameter in providing the global excitation state of a central core of M1 neurons.11 Accordingly, rMT is increased by drugs blocking the voltage-gated sodium channels, where the same drugs may not have an effect on the gamma-aminobutyric acid (GABA)-ergic functions. In contrast, rMT is reduced by drugs increasing glutamatergic transmission not mediated by the N-methyl-D-aspartate (NMDA) receptors, suggesting that rMT reflects both neuronal membrane excitability and non-NMDA receptor glutamatergic neurotransmission.12 Finally, the MT increases, being often undetectable, when a substantial portion of M1 or the cortico-spinal tract is damaged (i.e. by stroke or motor neuron disease), and decreases when the motor pathway is hyperexcitable (such as epilepsy).13
Repetitive (rTMS) is a specific stimulation paradigm characterized by the administration of a sequence of consecutive stimuli on the same cortical region, at different frequencies and inter sequence intervals. As known, rTMS can transiently modulate the excitability of the stimulated cortex, with both local and remote effects outlasting the stimulation period. Conventional rTMS modalities include high-frequency (HF-rTMS) stimulation (>1 Hz) and low-frequency (LF-rTMS) stimulation (⩽1 Hz).11 High-frequency stimulation typically increases motor cortex excitability of the stimulated area, whereas low-frequency stimulation usually produces a decrease in excitability.14 The mechanisms by which rTMS modulates the brain are rather complex, although they seem to be related to the phenomena of long-term potentiation (LTP) and long-term depression (LTD).15
When applied after a stroke, rTMS should ideally be able to suppress the so called ‘maladaptive plasticity’16,17 or to enhance the adaptive plasticity during rehabilitation. These goals can be achieved by modulating the local cortical excitability or modifying connectivity within the neuronal networks.10
rTMS in stroke rehabilitation: an overview
According to the latest International Federation of Clinical Neurophysiology (IFCN) guidelines on the therapeutic use of rTMS,10 there is a possible effect of LF-rTMS of the contralesional motor cortex in post-acute motor stroke, and a probable effect in chronic motor stroke. An effect of HF-rTMS on the ipsilesional motor cortex in post-acute and chronic motor stroke is also possible.
The potential role of rTMS in gross motor function recovery after a stroke has been assessed in a recent comprehensive systematic review of 70 studies by Dionisio and colleagues.18 The majority of the publications reviewed report a role of rTMS in improving motor function, although some randomized controlled trials (RCTs) were not able to confirm this result,19–23 as shown by a recent large randomized, sham-controlled, clinical trial of navigated LF-rTMS.24 It has also been suggested that rTMS can specifically improve manual dexterity,10 which is defined as the ability to coordinate the fingers and efficiently manipulate objects, and is of crucial importance for daily living activities.25 Notably, most of the studies focused on motor impairment in the upper limbs, whereas limited data is available on the lower limbs.18 Walking and balance are frequently impaired in stroke patients and significantly affect the quality of life (QoL),26,27 and rTMS might represent a valid aid in the recovery of these functions.28,29 Spasticity is another common complication after a stroke, consisting of a velocity-dependent increase of muscular tone,30 and for which rTMS has been proposed as a rehabilitation tool.31
Dysphagia is highly common in stroke patients, it impairs the global clinical recovery, and predisposes to complications.32 It has been pointed out that rTMS targeting the M1 area representing the muscles involved in swallowing may contribute to the treatment of post-stroke dysphagia.33
Nonmotor deficit is also a relevant post-stroke disability that negatively impacts the QoL. Aphasia is a very common consequence of stroke, affecting approximately 30% of stroke survivors and significantly limiting rehabilitation.34 According to the IFCN guidelines, to date, there is no recommendation for LF-rTMS of the contralesional right inferior frontal gyrus (IFG). Similarly, no recommendation for HF-rTMS or intermittent theta burst stimulation (TBS) of the ipsilesional left IFG or dorsolateral prefrontal cortex (DLPFC) in Broca’s aphasia has been currently approved.10 The same is true for LF-rTMS of the right superior temporal gyrus in Wernicke’s aphasia.10
Neglect is the incapacity to respond to tactile or visual contralateral stimuli that are not caused by a sensory-motor deficit.35 Although hard to treat, rTMS has been proposed as a tool for neglect rehabilitation.36 However, the IFCN guidelines state that currently there is no recommendation for LF-rTMS of the contralesional left posterior parietal cortex, or for HF-rTMS of the ipsilesional right posterior parietal cortex.10 In a recent systematic review, most of the included studies supported the use of TMS for the rehabilitation of aphasia, dysphagia, and neglect, although the heterogeneity of stimulation protocols did not allow definitive conclusions to be drawn.37
Post-stroke depression is a relevant complication of cerebrovascular diseases.38 The role of rTMS in the management of major depressive disorders is well documented,39,40 and currently, rTMS is internationally approved and indicated for the treatment of major depression in adults with antidepressant medication resistance, and in those with a recurrent course of illness, or in cases of moderate-to-severe disease severity.39 In major depression disorders, according to the IFCN guidelines, there is a clear antidepressant effect of HF-rTMS over the left DLPFC, a probable antidepressant effect of LF-rTMS on the right DLPFC, and probably no differential antidepressant effect between right LF-rTMS and left HF-rTMS. Moreover, there is currently no recommendation for bilateral stimulation combining HF-rTMS of the left DLPFC and LF-rTMS of the right DLPFC. The mentioned guidelines also state that the antidepressant effect when stimulating DLPFC is probably additive, and possibly potentiating, to the efficacy of antidepressant drugs.10 However, no specific recommendation currently addresses the use of rTMS in post-stroke depression. Recently, rTMS has been proposed as a treatment option for the late-life depression associated with chronic subcortical ischemic vascular disease, the so called ‘vascular depression’.41–44 Three studies tested rTMS efficacy in vascular depression (one was a follow-up study with citalopram). Although presenting positive findings, further trials should refine clinical and diagnostic criteria to assess its impact on antidepressant efficacy.45
Approximately 25–30% of stroke patients develop an immediate or delayed cognitive impairment or an overt picture of vascular dementia.46 There is evidence of an overall positive effect on cognitive function for both LF-rTMS47 and HF-rTMS,48 supported by studies on experimental models of vascular dementia.49–52 Nonetheless, the few trials examining the effect on stroke-related cognitive deficit produced mixed results.53–56 In particular, two studies found no effect on cognition when stimulating the left DLPFC at 1 Hz and 10 Hz,53,54 whereas a pilot study found a positive effect on the Stroop interference test with HF-rTMS over the left DLPFC in patients with vascular cognitive impairment without dementia.55 However, this finding was not replicated in a follow-up study.56 To summarize, rTMS can induce beneficial effects on specific cognitive domains, although data are limited and their clinical significance needs to be further validated. Major challenges exist in terms of appropriate patient selection and optimization of the stimulation protocols.57
Central post-stroke pain (CPSP) is the pain resulting from an ischemic lesion of the central nervous system.58 It represents a relatively common complication after a stroke, although it is often under-recognized and, therefore, undertreated.59 According to the IFCN guidelines for the use of rTMS in the treatment of neuropathic pain, there is a definite analgesic effect of HF-rTMS of contralateral M1 to the pain side, and LF-rTMS of contralateral M1 to the pain side is probably ineffective. In addition, there is currently no recommendation for cortical targets other than contralateral M1 to the pain side.10 Notably, rTMS might be effective in drug-resistant CPSP patients.58 A recent systematic review that included nine HF-rTMS studies suggested an effect on CPSP relief, but also underlined the insufficient quality of the studies considered.60
In this article, we aim to provide an up-to-date overview of the most recent evidence on the efficacy of rTMS in the rehabilitation of stroke patients. Although several studies have been published, a conclusive statement supporting a systematic use of rTMS in the multifaceted clinical aspects of stroke rehabilitation is still lacking.
•NIBS improved deficits in functional balance and postural control post stroke.
•The treatment effects on postural imbalance were significant following rTMS.
•The improvements after rTMS appeared in acute, subacute, and chronic patients.
•A higher number of rTMS sessions significantly increased the treatment effects.
The postural imbalance post stroke limits individual’s walking abilities as well as increase the risk of falling. We investigated the short-term treatment effects of non-invasive brain stimulation (NIBS) on functional balance and postural control in patients with stroke.
We started the search via PubMed and ISI’s Web of Science on March 1, 2019 and concluded the search on April 30, 2019.
The meta-analysis included studies that used either repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) for the recovery of functional balance and postural control post stroke. All included studies used either randomized control trial or crossover designs with a sham control group.
Three researchers independently performed data extraction and assessing methodological quality and publication bias. We calculated overall and individual effect sizes using random effects meta-analysis models.
The random effects meta-analysis model on the 18 qualified studies identified the significant positive effects relating to NIBS in terms of functional balance and postural control post stroke. The moderator variable analyses revealed that these treatment effects were only significant in rTMS across acute/subacute and chronic stroke patients whereas tDCS did not show any significant therapeutic effects. The meta-regression analysis showed that a higher number of rTMS sessions was significantly associated with more improvements in functional balance and postural control post stroke.
Our systematic review and meta-analysis confirmed that NIBS may be an effective option for restoring functional balance and postural control for patients with stroke.
A new review, which appears in The BMJ journal, examines the benefits of non-invasive brain stimulation for treating major depression and finds that the technique is a valid alternative to existing treatments.
Doctors should consider brain stimulation as an alternative treatment for people living with severe depression, finds a new review
Over 17 million adults in the United States have had an episode of major depression at one point in their lives.
Some of these people have treatment-resistant depression, which means common prescription drugs do not alleviate the symptoms.
Recent studies have pointed to alternative treatment methods for major depression, such as non-invasive brain stimulation techniques.
For instance, a study that appeared at the end of last year showed that using small electric currents to stimulate a brain area called the orbitofrontal cortex significantly improves the mood of people who did not benefit from conventional antidepressants.
An even more recent trial of a form of brain stimulation called “transcranial alternating current stimulation” (tACS) found that the technique halved depression symptoms in almost 80 percent of the study participants.
Despite such promising results, doctors do not use these techniques widely, as there is not enough data available on their efficacy.
So, a team of researchers led by Julian Mutz at the Institute of Psychiatry, Psychology & Neuroscience at King’s College London, United Kingdom, set out to review some clinical trials that have examined the benefits of non-invasive brain stimulation techniques for people living with depression.
Brain stimulation as additional treatment
Specifically, Mutz and team examined the results of 113 clinical trials. Overall, these trials included 6,750 participants who were 48 years old, on average, and were living with major depressive disorder or bipolar depression.
The original clinical trials involved randomly assigning these participants to 18 treatment interventions or “sham” therapies. The reviewers focussed on the response, or “efficacy” of the treatment, as well as the “discontinuation of treatment for any reason” — or “acceptability” of the therapies. Mutz and colleagues also rated the trials’ risk of bias.
The therapies included in the review were “electroconvulsive therapy (ECT), transcranial magnetic stimulation (repetitive (rTMS), accelerated, priming, deep, and synchronized), theta burst stimulation, magnetic seizure therapy, transcranial direct current stimulation (tDCS), or sham therapy.”
Of these, the treatments that the researchers in the original trial examined most often were high frequency left rTMS and tDCS, which they tested against sham therapy. On the other hand, not many trials covered more recent forms of brain stimulation, such as magnetic seizure therapy and bilateral theta burst stimulation, the review found.
Kutz and his team deemed 34 percent of the trials they reviewed as having a low risk of bias. They considered half of the trials to have an “unclear” risk of bias, and finally, 17 percent to have a high risk of bias. The newer the treatments, the higher was the uncertainty of the trials’ results.
The review found that bitemporal ECT, high dose right unilateral ECT, high frequency left rTMS and tDCS were all significantly more effective than sham therapy both in terms of efficacy and acceptability.
When considering “discontinuation of treatment for any reason,” the researchers found that the participants were not any likelier to discontinue brain stimulation treatments than they were sham therapy. Mutz and colleagues conclude:
“These findings provide evidence for the consideration of non-surgical brain stimulation techniques as alternative or add-on treatments for adults with major depressive episodes.”
“These findings also highlight important research priorities in the specialty of brain stimulation, such as the need for further well-designed randomized controlled trials comparing novel treatments, and sham-controlled trials investigating magnetic seizure therapy,” the authors add.
Finally, the researchers also note that their results have clinical implications, “in that they will inform clinicians, patients, and healthcare providers on the relative merits of multiple non-surgical brain stimulation techniques.”
The aim of this study was to evaluate the effects of repetitive transcranial magnetic stimulation (rTMS) on the post-stroke recovery of lower limb motor function.
We searched the databases of PubMed, Cochrane Library, and Embase. The randomized controlled trials were published by 25 January 2019.
We included randomized controlled trials that evaluated the effects of rTMS on lower limb motor recovery in patients with stroke. Two reviewers independently screened the searched records, extracted data, and assessed the risk of bias. The treatment effect sizes were pooled in a meta-analysis by using the RevMan 5.3 software. The internal validity was assessed using topics suggested by the Physiotherapy Evidence Database (PEDro).
Eight studies with 169 participants were included in the meta-analysis. Pooled estimates demonstrated that rTMS significantly improved the body function of the lower limbs (standardized mean difference (SMD) = 0.66; P < 0.01), lower limb activity (SMD = 0.66; P < 0.01), and motor-evoked potential (SMD = 1.13; P < 0.01). The subgroup analyses results also revealed that rTMS improved walking speed (SMD = 1.13) and lower limb scores on the Fugl-Meyer Assessment scale (SMD = 0.63). We found no significant differences between the groups in different mean post-stroke time or stimulation mode over lower limb motor recovery. Only one study reported mild adverse effects.
rTMS may have short-term therapeutic effects on the lower limbs of patients with stroke. Furthermore, the application of rTMS is safe. However, this evidence is limited by a potential risk of bias.
The primary aim of this meta-analysis was to evaluate the effects of repetitive transcranial magnetic stimulation (rTMS) on limb movement recovery post-stroke and cortex excitability, to explore the optimal parameters of rTMS and suitable stroke population. Second, adverse events were also included.
The databases of PubMed, EBSCO, MEDLINE, the Cochrane Central Register of Controlled Trials, EBM Reviews-Cochrane Database, the Chinese National Knowledge Infrastructure, and the Chinese Science and Technology Journals Database were searched for randomized controlled trials exploring the effects of rTMS on limb motor function recovery post-stroke before December 2018.
The effect sizes of rTMS on limb motor recovery, the effect size of rTMS stimulation parameters, and different stroke population were summarized by calculating the standardized mean difference (SMD) and the 95% confidence interval using fixed/random effect models as appropriate.
For the motor function assessment, 42 eligible studies involving 1168 stroke patients were identified. The summary effect size indicated that rTMS had positive effects on limb motor recovery (SMD = 0.50, P < 0.00001) and activities of daily living (SMD = 0.82, P < 0.00001), and motor-evoked potentials of the stimulated hemisphere differed according to the stimulation frequency, that is, the high-frequency group (SMD = 0.57, P = 0.0006), except the low-frequency group (SMD = –0.27, P = 0.05). No significant differences were observed among the stimulation parameter subgroups except for the sessions subgroup (P = 0.02). Only 10 included articles reported transient mild discomfort after rTMS.
rTMS promoted the recovery of limb motor function and changed the cortex excitability. rTMS may be better for early and pure subcortical stroke patients. Regarding different stimulation parameters, the number of stimulation sessions has an impact on the effect of rTMS.
We reported the case of a patient WLX, who had one ischemic stroke more than 3 years ago, and had underwent intermittent rehabilitation since then. He still had profound right upper limb paralysis and moderate spasm, accompanied with non-fluent aphasia when came to our department; and complained that his recovery had been rather slow for about two years. In addition to the custom rehabilitation, we applied a peripheral plus central rTMS paradigm to him, which included 3 sessions of peripheral magnetic stimulation to his paralyzed right forearm, followed by a session of high frequency rTMS to the bilateral sensorimotor cortex region. The total magnetic stimulation therapy lasted about 30 min a day, and was applied 5 days/week for 4 weeks.
After 4 weeks’ treatment, the patient’s Fulg–Meyer upper limb assessment (FMA) score was obviously improved (from 27 to 37 points), and the spasm was largely relieved in his right hand and arm.
Peripheral plus central rTMS might be an effective treatment for motor dysfunction of chronic stroke patients.
•1-Hz repetitive transcranial magnetic stimulation with rehabilitation immediately after botulinum toxin type A injection in a stroke patient.
•The spasticity, motor function, and usefulness of the paretic hand improved.
•This is a possibility of shortening the intervention period of combined therapy.
Single case report.
A previous study clarified that spasticity and motor function were improved by combined treatment with botulinum toxin type A (BTX) injection and 1-Hz repetitive transcranial magnetic stimulation (rTMS) with intensive motor training at 4 weeks after injection. However, it is not clear whether 1-Hz rTMS with intensive motor training immediately after BTX injection also improves spasticity and motor function in stroke patients.
Purpose of the Case Report
The purpose of this case report is to test the short- and long-term effects of BTX injection and rTMS with intensive motor training on the spasticity, motor function, and usefulness of the paretic hand in a stroke patient.
A 64-year-old male, who suffered from a right cerebral hemorrhage 53 months previously, participated in the present study. BTX was injected into the spastic muscles of the affected upper limb. He then received the new protocol for a total of 24 sessions. The Modified Ashworth Scale (MAS), Fugl-Meyer Assessment (FMA), and Motor Activity Log, consisting of the amount of use and quality of movement scales, were assessed before and immediately after BTX injection, at discharge, and monthly for up to 5 months after discharge.
For the short-term effects of the therapy, the MAS scores of the elbow and wrist, FMA score, and quality of movement score improved. For the long-term effects of the therapy, the MAS score of the fingers, FMA score, and amount of use score improved for up to 5 months after discharge.
The present case report showed the improvement of all assessments performed in the short and/or long term and suggest the possibility of shortening the intervention period of combined therapy of BTX and rTMS with intensive motor training.
A better understanding of the neural substrates that underlie motor recovery after stroke has led to the development of innovative rehabilitation strategies and tools that incorporate key elements of motor skill relearning, that is, intensive motor training involving goal-oriented repeated movements. Robotic devices for the upper limb are increasingly used in rehabilitation. Studies have demonstrated the effectiveness of these devices in reducing motor impairments, but less so for the improvement of upper limb function. Other studies have begun to investigate the benefits of combined approaches that target muscle function (functional electrical stimulation and botulinum toxin injections), modulate neural activity (noninvasive brain stimulation), and enhance motivation (virtual reality) in an attempt to potentialize the benefits of robot-mediated training. The aim of this paper is to overview the current status of such combined treatments and to analyze the rationale behind them.
Significant advances have been made in the management of stroke (including prevention, acute management, and rehabilitation); however cerebrovascular diseases remain the third most common cause of death and the first cause of disability worldwide [1–6]. Stroke causes brain damage, leading to loss of motor function. Upper limb (UL) function is particularly reduced, resulting in disability. Many rehabilitation techniques have been developed over the last decades to facilitate motor recovery of the UL in order to improve functional ability and quality of life [7–10]. They are commonly based on principles of motor skill learning to promote plasticity of motor neural networks. These principles include intensive, repetitive, task-oriented movement-based training [11–19]. A better understanding of the neural substrates of motor relearning has led to the development of innovative strategies and tools to deliver exercise that meets these requirements. Treatments mostly target the neurological impairment (paresis, spasticity, etc.) through the activation of neural circuits or by acting on peripheral effectors. Robotic devices provide exercises that incorporate key elements of motor learning. Advanced robotic systems can offer highly repetitive, reproducible, interactive forms of training for the paretic limb, which are quantifiable. Robotic devices also enable easy and objective assessment of motor performance in standardized conditions by the recording of biomechanical data (i.e., speed, forces) [20–22]. This data can be used to analyze and assess motor recovery in stroke patients [23–26]. Since the 1990s, many other technology-based approaches and innovative pharmaceutical treatments have also been developed for rehabilitation, including virtual reality- (VR-) based systems, botulinum neurotoxin (BoNT) injections, and noninvasive brain stimulation (NIBS) (Direct Current Stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS)). There is currently no high-quality evidence to support any of these innovative interventions, despite the fact that some are used in routine practice . By their respective mechanisms of action, each of these treatments could potentiate the effects of robotic therapy, leading to greater improvements in motor capacity. The aim of this paper is to review studies of combined treatments based on robotic rehabilitation and to analyze the rationale behind such approaches.[…]