FYI.
Yu-Feng Chen1,2,

Guang-Yue Zhu
3,
Meng-Chai Mao1,4,

Ya Zheng
3,

Hao Huang
5,

Lan-Lan Liu
5,
Si-Yun Chen1,
Ling-Yun Cao1 and
Dong-Sheng Xu1,4,6*
- 1School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- 2Department of Tui Na, Hangzhou Dingqiao's Hospital, Hangzhou, China
- 3Rehabilitation Medical Center, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai, China
- 4Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Shanghai, China
- 5Department of Rehabilitation Medicine,
Shanghai Third Rehabilitation Hospital Affiliated to Shanghai University
of Traditional Chinese Medicine, Shanghai, China
- 6Department of Rehabilitation Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China
Upper limb motor dysfunction after stroke is a serious threat to the
living quality of patients and their families. Recovery of upper limb
motor function after stroke largely relies on the activation and
remodeling of neural circuits. rTMS (repetitive transcranial magnetic
stimulation) has been proved to promote the reconstruction of neural
synapses and neural circuits. However, there are still a large number of
patients who cannot fully recover and leave behind varying degrees of
dysfunction. Considering the systemic pathology after stroke, in
addition to focal brain injury, stroke can also cause extensive
dysfunction of peripheral organs. The rehabilitation strategy for stroke
should combine the treatment of primary brain lesions with the
intervention of secondary systemic damage. The aim of this trial is to
verify the efficacy of rTMS synergize with Tui Na (Chinese Massage) on
upper limb motor function after ischemic stroke, and to explore the
mechanism of activation and remodeling of sensorimotor neural circuits
with functional near-infrared spectroscopy. Ninety patients will be
randomly assigned to either rTMS + Tui Na + conventional rehabilitation
group (the experimental group) or rTMS + conventional rehabilitation
group (the control group) in 1:1 ratio. Intervention is conducted five
sessions a week, with a total of twenty sessions. The primary outcome is
Fugl-Meyer Assessment, and the secondary outcomes include Muscle
Strength, Modified Ashworth Assessment, Modified Barthel Index
Assessment, motor evoked potentials and functional near-infrared
spectroscopy. There are four time points for the evaluation, including
baseline, 2 weeks and 4 weeks after the start of treatment, and 4 weeks
after the end of treatment. This study is a randomized controlled trial.
This study was approved by Institutional Ethics Committee of Shanghai
Third Rehabilitation Hospital Affiliated to Shanghai University of
Traditional Chinese Medicine (approval No. SH3RH-2021-EC-012) on
December, 16th, 2021. The protocol was registered with Chinese Clinical
Trial Registry (ChiCTR2200056266), on February 3th, 2022. Patient
recruitment was initiated on February 10th, 2022, and the study will be
continued until December 2023.
Background
Epidemiological investigation shows that stroke seriously threatens safety and quality of life in the world (1).
Ischemic stroke accounts for a higher proportion than that of
hemorrhagic stroke. Most patients have motor dysfunction, especially
upper limb (UL) motor dysfunction after stroke (2).
UL movement is more delicate and complex, and its unsatisfactory
recovery can reduce patients' activities of daily life and seriously
affect the living quality of patients and their families (3). Therefore, UL motor dysfunction is a key and challenging point in rehabilitation after stroke.
Transcranial magnetic stimulation (TMS) is a
neuromodulation technique for treating nervous and mental diseases in
recent years. Repetitive transcranial magnetic stimulation (rTMS) is a
continuous, repetitive mode of TMS, and it has been proved that rTMS has
a good effect on neurological disorders. The latest guideline in 2019
recommended TMS as an A level for treating UL motor dysfunction in
subacute stroke (4).
Research has shown that rTMS can promote the regulation of
microenvironmental factors, glial cell activity, and nerve fiber myelin
sheath repair in the injured area, and promote the reconstruction of
neural synapses and neural circuits (5–7).
However, there are still a large number of patients who cannot fully
recover and leave behind varying degrees of dysfunction (8).
Therefore, while continuously improving the technology of rTMS, such as
accuracy and treatment depth, it is necessary to find other methods to
synergize with rTMS to enhance the therapeutic effect. Currently, there
are some deficiencies in the combination between rTMS and other
treatments (such as neuromuscular electrical stimulation, physical
therapy and occupational therapy). The treatment mainly focuses on the
brain and limbs, but does not pay attention to the influence of systemic
pathology on the recovery of UL, and there is no good intervention
method for systemic pathological injury (9).
Considering the systemic pathology after stroke, in
addition to focal brain injury, stroke can also cause extensive
dysfunction of peripheral organs. Stroke will profoundly change the
autonomic nervous system, hypothalamus-pituitary-adrenal axis, immune
system and fascia and muscle system, resulting in further systemic
damage (10).
In turn, systemic pathological changes after stroke promote the
progress and prognosis of brain injury to a great extent. Especially in
the elderly, it usually leads to more serious systemic damage and a
worse prognosis after stroke (9).
Before the stroke, the central and peripheral organ systems of a large
number of elderly patients have been affected by varying degrees of
structural and functional degradation because of continuous exposure to
normal aging or chronic low-grade systemic inflammation and other
pathological backgrounds. All of these “silent” pathology before stroke
have laid the foundation for the emergence of systemic abnormalities
caused by stroke (9).
After the stroke, excitotoxicity, neuroinflammation, energy
disturbance, oxidative stress, and other pathological processes work
together, combined with previous complications, to cause or aggravate
the structural changes and functional damage of multiple peripheral
organs (11).
Therefore, stroke should be regarded as a systemic disease with a
profound impact on the surrounding organs. The rehabilitation strategy
for stroke should combine the treatment of primary brain lesions with
the intervention of secondary systemic damage.
Tui Na (Chinese massage therapy) is a relatively simple,
inexpensive and non-invasive intervention, and has been used to treat
stroke patients for many years in China(appeal to antiquity is not valid). Tui Na mainly acts on specific
parts of the body through manipulation, on the one hand, it plays a
local therapeutic role in the body, on the other hand, it can also have a
certain impact on various systems of the body through nerves, body
fluids and other ways, so as to achieve the role of treating diseases (12). Clinical observation suggested that Tui Na might be a safe and effective treatment for post-stroke UL motor dysfunction (13, 14).
Although the mechanism of Tui Na on treatment of post-stroke motor
dysfunction is limited, some possible mechanism was proposed. Tui Na
manipulation stretched the muscle–tendon complex and stimulate the Golgi
tendon organ that could inhibit alpha motor neurons and reduce spasm (15).
Tui Na manipulation might reinforce sensory stimulation and activate
the gamma efferent fibers of muscle stretch receptors that make
receptors more sensitive to stretch (15).
Soreness and distension that was caused by Tui Na manipulation will
excite the sensory cortex, thus inhibit reticular formation of brainstem
and decrease the muscle tone (15).
For more than two thousand years, traditional Chinese medicine
therapists have been using Tui Na act on governor meridian-related
acupoints to treat spinal-related diseases and many visceral disorders (16).
The spine is the pillar of the human body and the medium that connects
the brain and the peripheral organs. The spine is the pathway of the
governor meridian in traditional Chinese medicine, which dominates
people's life activities (17).
The spine contains the spinal cord, with spinal nerves and sympathetic
pathways on both sides. Although there are great differences in theory
and technology between traditional Chinese and western medicine, they
are almost the same in understanding the importance of the spine and
preventing and treating diseases by adjusting the spine and its related
surrounding tissues.
Based on the above research background, we adopt the
strategy of rTMS to synergize with Tui Na to promote the recovery of UL
motor dysfunction after ischemic stroke. fNIRS (functional near-infrared
spectroscopy) will be used as a technique for sensorimotor cortex
activity monitoring and brain plasticity evaluation. The function of Tui
Na is reflected in two aspects:1. Tui Na will be used to stimulate the
peripheral sensory nerve, promote the activation of the cortical
sensorimotor network, and then activate the corticospinal tract with
rTMS from the cortical motor area (M1) aimed at the reconstruction of
“sensory afferent-cortical integration-motor execution,” in order to
obtain the effect of synergy-enhancement. 2. The extensive effects of
Tui Na on autonomic nerve, fascia and muscle system can promote the
function of a wide range of peripheral organs, to promote the prognosis
of stroke. Therefore, our primary objective was to identify a protocol
for a randomized controlled trial to evaluate the effects of rTMS
synergizing with Tui Na on the motor function of the UL in patients with
ischemic stroke. We hypothesized that the treatment of rTMS synergized
with Tui Na can promote the improvement of UL motor function after
ischemic stroke and activate and remodel sensorimotor cortex activity.