Stroke
is a leading cause of death and disability worldwide, with impaired
upper limb motor function being a common outcome for stroke survivors.
According to the Global Burden of stroke 2019, stroke had become the
second most common causes of death (11.6% of all deaths [95% uncertainty
interval, 10.8–12.2%]) and the third most common causes of disability
(5.7% of disability-adjusted life years from all causes [95% uncertainty
interval, 5.1–6.2]) in the world [1].
Among people experiencing stroke episodes, impaired motor function of
upper extremities often had adverse effects on the daily activities [2] and participation [3]. In 70% of stroke patients, upper limb involvement was responsible for long-term impairment of daily function and activities [4, 5].
Even
with traditional neurorehabilitation programs, approximately 50–60% of
stroke patients still experience chronic motor limitations [6].
To address this, non-invasive brain stimulation such as central theta
burst stimulation (TBS), a novel form of repetitive transcranial
magnetic stimulation (rTMS), have been used to treat these patients [7]. Central TBS has been found to have persistent effects on motor evoked potentials (MEPs) [8, 9]. The bimodal balance-recovery model has been proposed as the underlying mechanism for central rTMS [10].
This model combined the concepts of interhemispheric competition and
vicariation effects of the intact hemisphere in patients with stroke [10].
The hypothesis posited that there was a reduction in cortical
excitability within the impaired hemisphere, accompanied by an increase
in transcallosal inhibitory signaling originating from the intact
hemisphere [10].
To facilitate cortical excitability in the impaired hemisphere,
intermittent TBS (iTBS) is applied, while continuous TBS (cTBS) is
utilized to reduce transcallosal inhibitory signals in the intact
hemisphere [11].
A recent meta-analysis has shown that iTBS outperforms cTBS in terms of
promoting upper limb motor recovery in stroke patients [12]. Therefore, iTBS was selected for this study.
Repetitive
peripheral magnetic stimulation (rPMS) is another non-invasive brain
stimulation technique that targets the peripheral motor nerve through
both direct and indirect activation [13,14,15].
The transmission of direct activation occurred through the sensorimotor
nerve, whereas indirect activation was facilitated by the
mechanoreceptor nerve [13,14,15]. It has been hypothesized that rPMS could induce neuroplasticity and cortical reorganization [13,14,15].
Prior research has demonstrated increased motor evoked potential (MEP)
amplitudes in the upper limb following rPMS application [16,17,18,19]. One study demonstrated the potential of rPMS to enhance distal motor function [20], and another showed its effectiveness in improving proximal muscle strength in early subacute stroke patients [21].
Recent studies further underscore the positive impact of rPMS on upper
motor function assessed by Fugl-Meyer Assessment (FMA) during the
subacute and acute phases of stroke [21, 22]. Furthermore, FMA-Upper Extremity (FMA-UE) includes proximal and distal domain [23, 24]. Considering
that most patients with stroke suffered from flexor spasticity in the
upper limb, which limited their ability to open hands for object
manipulation. Thus, we chose the radial nerve for the delivery of rPMS,
which is essential for the recovery of skilled hand prehension [25].
To date, the majority of studies have focused on the effects of integrating rPMS with rehabilitation programs [20,21,22]
for patients with stroke. Currently, one study showed that central rTMS
combined with rPMS altered cerebellar and frontoparietal cortical
activity via functional magnetic images [26]. One study combined rTMS with rPMS to improved patient’s spasticity and motor function [27]. While the individual benefits of central rTMS and rPMS have been documented in previous studies [26, 27],
our rationale for combining them is based on emerging evidence that
rPMS can modulate motor cortical excitability in the central nervous
system [13,14,15]. Furthermore, the iTBS was proved to have more enduring effects than the conventional rTMS [2, 28].
This concept is still relatively novel, and no studies have explored
the synergistic effects of central iTBS when combined with peripheral
rPMS. Therefore, we hypothesized that applying rPMS to the radial nerve
might enhance the effectiveness of central iTBS over the primary motor
cortex, leading to improvement in motor function, activities, and
participation. This is the first randomized controlled trial
investigating the synergistic efficacy of rPMS on central iTBS in
treating upper limb dysfunction in patients with stroke.
More at link.
Junle Zhao
Mingjie Chen
Junning Mo
Yutong Zhong
Jiamin Qiu
Yanjiao Qiu
Youjia Li
Xiaoyan Han