Efficacy and Safety of High-Dose TBS on Poststroke Upper Extremity Motor Impairment: A Randomized Controlled Trial

Abstract

Background: Upper extremity (UE) motor function impairment is a major poststroke complication whose recovery remains one of the most challenging tasks in neurological rehabilitation. This study examined the efficacy and safety of the personalized neuroimaging-guided high-dose theta-burst stimulation (TBS) for poststroke UE motor function recovery.

Methods: Patients after stroke with UE motor impairment from a China rehabilitation center were randomly assigned to receive high-dose intermittent TBS (iTBS) to ipsilesional UE sensorimotor network, continuous TBS (cTBS) to contralesional UE sensorimotor network, or sham stimulation, along with conventional therapy for 3 weeks. The primary outcome was the score changes on the Fugl-Meyer assessment-UE from baseline to 1 and 3 weeks. The secondary outcomes included the response rate on Fugl-Meyer assessment-UE scores posttreatment (≥9-point improvement) and score changes in multidimensional scales measuring UE, lower extremity, and activities and participation.

Results: From June 2021 to June 2022, 45 participants were randomized and 43 were analyzed. The iTBS and continuous TBS groups showed significantly greater improvement in Fugl-Meyer assessment-UE (mean improvement, iTBS: 10.73 points; continuous TBS: 10.79 points) than the sham group (2.43 points) and exhibited significantly greater response rates on Fugl-Meyer assessment-UE (iTBS, 60.0%; continuous TBS, 64.3%) than the sham group (0.0%). The active groups consistently exhibited superior improvement on the other 2 UE assessments at week 3. However, only the iTBS group showed greater efficacy on 1 lower extremity assessment than the sham group at week 3. Both active groups showed significant improvements in activities and participation assessments.

Conclusions: The study provides evidence for the efficacy and safety of high-dose TBS in facilitating poststroke UE rehabilitation.

Registration: URL: www.chictr.org.cn; Unique identifier: ChiCTR2100047340.

Keywords: magnetic resonance imaging; neurological rehabilitation; stroke; transcranial magnetic stimulation; upper extremity.

Figure 1.

The schematic illustrates neuroimaging-guided target identification for stimulation. The upper figure displays the upper extremity sensorimotor network (UESN) identification using individualized functional parcellation. The lower figure shows the individual target location process. Brain maps from a participant with left frontal lobe hemorrhage are displayed. A, Participant underwent structural and functional magnetic resonance imaging (MRI) before allocation. The red rectangles highlight the lesion’s location and size. B, Functional parcellation was generated using a group-level atlas and an interindividual variability map, with a confidence value assigned to each vertex. C, Refined UESN from individual parcellation. D, Confidence value and sulcal depth are used for determining ideal stimulation targets within the UESN. Search areas with high confidence values in the UESN are shown in both hemispheres (top), while the sulcal depth maps highlight the cerebral cortex’s folding pattern (bottom)—warm colors indicate sulci and cold indicate gyri. E, Stimulation targets in both hemispheres are identified, marked with red arrows. F, Participants, blinded to their group assignment, were randomized into 3 groups and began intervention after resting motor threshold (RMT) measurement. BOLD indicates blood oxygenation level-dependent; cTBS, continuous theta-burst stimulation; and iTBS, intermittent theta-burst stimulation.

Figure 2.

The flow diagram of the trial. Participant identification was facilitated through physician referrals and hospital advertisements, yielding 76 prescreened referrals. Further exclusions were mainly based on magnetic resonance imaging eligibility and other reasons. cTBS indicates continuous theta-burst stimulation; and iTBS, intermittent theta-burst stimulation.

Figure 3.

Treatment effects of intermittent theta-burst stimulation (iTBS), continuous theta-burst stimulation (cTBS), and sham stimulation as reflected by the Fugl-Meyer assessment-upper extremity (FMA-UE) and other multidimensional assessments. A, Mean FMA-UE score changes at T0, T1, and T2 for iTBS, cTBS, and sham groups. Both iTBS and cTBS significantly outperformed sham at T1 and T2. B, The number of participants who responded on FMA-UE (minimal clinically important difference ≥9-point) at T2 was significantly higher in the iTBS (60.0%, 9/15) and cTBS (64.3%, 9/14) groups than in the sham group (0.0%, 0/14). C, For chronic subgroup patients (>3 months after stroke), cTBS consistently outperformed sham (corrected P=0.018), while iTBS improvements were not significant after correction (uncorrected P=0.044; corrected P=0.088). D, A radar plot shows score changes from T0 to T2 in UE, lower extremity (LE), and activities and participation (AP) assessments. iTBS and cTBS showed greater improvements in UE and AP than sham, but results were inconsistent for LE assessments. Error bars indicate SE. *Comparisons between iTBS and sham; ^∆comparisons between cTBS and sham; */^∆P<0.05; **/^∆∆P<0.01; and ***/^∆∆∆P<0.001. FAC indicates functional ambulation category; GS, grip strength; MBI, modified Barthel index; SIS, Stroke Impact Scale; and WMFT, Wolf Motor Function Test.