Effectiveness of cerebellar vermis intermittent theta-burst stimulation in improving trunk control and balance function for patients with subacute stroke: a randomised controlled trial protocol.

INTRODUCTION: Balance impairments frequently occur after stroke. Achieving effective core trunk stability is the key to improving balance ability. However, there is still a lack of advanced well-defined rehabilitation protocols for balance improvement in patients with stroke. Intermittent theta-burst stimulation (iTBS) is a non-invasive brain activity modulation strategy that can produce long-term potentiation. The cerebellar vermis is a fundamental structure involved in balance and motor control. However, no study has demonstrated the therapeutic effect and potential mechanism of cerebellar vermis iTBS on balance after stroke. METHODS AND ANALYSIS: This study will be a prospective single-centre double-blind randomised controlled clinical trial with a 3-week intervention and 3-week follow-up. Eligible participants will be randomly allocated to the experimental group or the control group in a 1:1 ratio. After routine conventional physical therapy, patients in the experimental group will receive cerebellar vermis iTBS, whereas patients in the control group will receive sham stimulation. The overall intervention period will be 5 days a week for 3 consecutive weeks. The outcomes will be measured at baseline (T0), 3 weeks postintervention (T1) and at the 3-week follow-up (T2). The primary outcomes are Berg Balance Scale and Trunk Impairment Scale scores. The secondary outcomes are balance test scores via the Balance Master system, muscle activation of the trunk and lower limbs via the surface electromyography recordings, cerebral cortex oxygen concentrations measured via the resting-state functional near-infrared spectroscopy, Fugl-Meyer Assessment of Lower Extremity and Barthel index scores. ETHICS AND DISSEMINATION: This study was approved by the West China Hospital Clinical Trials and Biomedical Ethics Committee of Sichuan University. All participants will sign the informed consent form voluntarily. The results of this study will be published in peer-reviewed journals and disseminated at academic conferences. TRIAL REGISTRATION NUMBER: ChiCTR2200065369.

The Immediate Effects of Intermittent Theta Burst Stimulation of the Cerebellar Vermis on Cerebral Cortical Excitability During a Balance Task in Healthy Individuals: A Pilot Study.

Objective: This pilot study aimed to investigate the immediate effects of single-session intermittent theta-burst stimulation (iTBS) on the cerebellar vermis during a balance task, which could unveil the changes of cerebral cortical excitability in healthy individuals. Subjects: A total of seven right-handed healthy subjects (26.86 ± 5.30 years) were included in this study. Interventions: Each subject received single-session iTBS on cerebellar vermis in a sitting position. Main Measures: Before and after the intervention, all subjects were asked to repeat the balance task of standing on the left leg three times. Each task consisted of 15 s of standing and 20 s of resting. Real-time changes in cerebral cortex oxygen concentrations were monitored with functional near-infrared spectroscopy (fNIRS). During the task, changes in blood oxygen concentration were recorded and converted into the mean HbO2 for statistical analysis. Results: After stimulation, the mean HbO2 in the left SMA (P = 0.029) and right SMA (P = 0.043) significantly increased compared with baseline. However, no significant changes of mean HbO2 were found in the bilateral dorsolateral prefrontal lobe (P > 0.05). Conclusion: Single-session iTBS on the cerebellar vermis in healthy adults can increase the excitability of the cerebral cortex in the bilateral supplementary motor areas during balance tasks. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [ChiCTR2100048915].

Cerebellar Intermittent Theta-Burst Stimulation Reduces Upper Limb Spasticity After Subacute Stroke: A Randomized Controlled Trial.

Objective: This study aims to explore the efficacy of cerebellar intermittent theta-burst stimulation (iTBS) on upper limb spasticity in subacute stroke patients. Methods: A total of 32 patients with upper limb spasticity were enrolled and randomly assigned to treatment with cerebellar iTBS or sham stimulation before conventional physical therapy daily for 2 weeks. The primary outcomes included the modified Ashworth scale (MAS), the modified Tardieu scale (MTS), and the shear wave velocity (SWV). The secondary outcomes were the H-maximum wave/M-maximum wave amplitude ratio (Hmax/Mmax ratio), motor-evoked potential (MEP) latency and amplitude, central motor conduction time (CMCT), and the Barthel Index (BI). All outcomes were evaluated at baseline and after 10 sessions of intervention. Results: After the intervention, both groups showed significant improvements in the MAS, MTS, SWV, and BI. In addition, patients treated with cerebellar iTBS had a significant increase in MEP amplitude, and patients treated with sham stimulation had a significant decrease in Hmax/Mmax ratio. Compared with the sham stimulation group, the MAS, MTS, and SWV decreased more in the cerebellar iTBS group. Conclusion: Cerebellar iTBS is a promising adjuvant tool to reinforce the therapeutic effect of conventional physical therapy in upper limb spasticity management after subacute stroke (Chinese Clinical Trial Registry: ChiCTR1900026516).

Cerebellar Theta Burst Stimulation on Walking Function in Stroke Patients: A Randomized Clinical Trial.

Objectives: The objective of this study was to explore the efficacy of cerebellar intermittent theta burst stimulation (iTBS) on the walking function of stroke patients. Methods: Stroke patients with walking dysfunction aged 25-80 years who had suffered their first unilateral stroke were included. A total of 36 patients [mean (SD) age, 53 (7.93) years; 10 women (28%)] were enrolled in the study. All participants received the same conventional physical therapy, including transfer, balance, and ambulation training, during admission for 50 min per day during 2 weeks (10 sessions). Every session was preceded by 3 min procedure of cerebellar iTBS applyed over the contralesional cerebellum in the intervention group or by a similar sham iTBS in control group. The groups were formed randomly and the baseline characteristics showed no significant difference. The primary outcome measure was Fugl-Meyer Assessment-Lower Extremity scores. Secondary outcomes included walking performance and corticospinal excitability. Measures were performed before the intervention beginning (T0), after the first (T1) and the second (T2) weeks. Results: The Fugl-Meyer Assessment for lower extremity scores slightly improved with time in both groups with no significant difference between the groups and over the time. The walking performance significantly improved with time and between group. Two-way mixed measures ANOVA showed that there was significant interaction between time and group in comfortable walking time (F 2,68 = 6.5242, P = 0.0080, η2 partial = 0.276, ε = 0.641), between-group comparisons revealed significant differences at T1 (P = 0.0072) and T2 (P = 0.0133). The statistical analysis of maximum walking time showed that there was significant interaction between time and groups (F 2,68 = 5.4354, P = 0.0115, η2 partial = 0.198, ε = 0.734). Compared with T0, the differences of maximum walking time between the two groups at T1 (P = 0.0227) and T2 (P = 0.0127) were statistically significant. However, both the Timed up and go test and functional ambulation category scale did not yield significant differences between groups (P > 0.05). Conclusion: Our results revealed that applying iTBS over the contralesional cerebellum paired with physical therapy could improve walking performance in patients after stroke, implying that cerebellar iTBS intervention may be a noninvasive strategy to promote walking function in these patients. This study was registered at ChiCTR, number ChiCTR1900026450.

Low-Frequency Vibration Promotes Tumor Necrosis Factor-α Production to Increase Cartilage Degeneration in Knee Osteoarthritis.

OBJECTIVE: Low-frequency vibration accelerates cartilage degeneration in knee osteoarthritis (KOA) rat model. In this article, we investigated whether whole-body vibration (WBV) increases cartilage degeneration by regulating tumor necrosis factor-α (TNF-α) in KOA. DESIGN: Proteomics analysis was used to filter candidate protein from synovial fluid (SF) in KOA people after WBV. Enzyme-linked immunosorbent assay (ELISA) was used to estimate changes in TNF-α levels in SF. The C57 mice and TNF-α knock-out mice were sacrificed for the KOA model and WBV intervention. The cartilage was tested by ELISA, histology, terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL), immunohistochemistry, and reverse transcriptase polymerase chain reaction. Luciferase activity test in vitro study was conducted to confirm the relationship between TNF-α and the candidate protein. RESULTS: Differentially expressed proteins were enriched in the glycolytic process, glucose catabolic, and regulation of interleukin-8 (IL-8) secretion processes. Phosphoglycerate kinase, triosephosphate isomerase 1, T cell immunoglobulin- and mucin-domain-containing molecules 2, fumarylacetoacetate hydrolase (FAH), and TNF were the hub node. TNF-α expression increased in SF after WBV (P < 0.05). The cartilage was more degenerated in the TNF-α-/- mice group compared to controls. A significant change was observed in collagen II and FAH (P < 0.05). TNF-α expression improved in C57 mice (P < 0.05). Apoptosis of chondrocytes was inhibited in TNF-α-/- mice by the TUNEL test. Luciferase activity significantly increased in TNF-α + FAH-Luc cells (P < 0.05). CONCLUSION: A novel mechanism underlying WBV-triggered cartilage degeneration was found in KOA that demonstrated the critical regulatory function of TNF-α and FAH during WBV.