The Impact of Neuronavigation in rTMS for Hemiplegic Stroke Patients.

This is a single-center, randomized, two-group parallel-assignment interventional trial conducted at Taichung Veterans General Hospital to compare the effectiveness of neuronavigation-guided rTMS versus conventional rTMS in subacute stroke patients with hemiparesis.

Background: Repetitive Transcranial Magnetic Stimulation (rTMS) is recognized for its potential in stroke rehabilitation, with low-frequency (1 Hz) stimulation over the unaffected motor cortex in the subacute phase rated as Grade A (definitely effective) for upper limb motor recovery. However, the efficacy of rTMS is highly dependent on accurate and consistent coil placement over the target cortical area.

Study Hypothesis: We hypothesize that using neuronavigation-which integrates infrared tracking with brain MRI to establish a precise 3D coordinate reference-will significantly increase the treatment precision, reduce the required localization time, and ultimately lead to superior clinical outcomes compared to conventional manual targeting methods.

Intervention Details:

1. Participants: 30 eligible patients (age 20-85) who are 2 weeks to 6 months post-stroke and demonstrate unilateral upper limb weakness will be enrolled.
2. Stimulation Parameters: All participants will receive low-frequency rTMS (1 Hz) at 80% of the motor threshold (RMT). Each session consists of 1,200 pulses delivered over approximately 20 minutes.
3. Grouping:

(1)Experimental Group (n=15): Coil positioning will be guided by a neuronavigational system throughout all 10 sessions. The system tracks the coil and patient's head relative to the initial M1 hotspot.

(2)Control Group (n=15): Coil positioning will rely on standard manual localization (e.g., cap positioning).

Outcome Assessments:

The study will track three primary outcomes: FMA score (a key measure of motor function), coil positioning deviation (a measure of precision), and the time required for initial hotspot localization. Secondary outcomes include functional and spasticity measures such as the Barthel Index (BI), Modified Rankin Scale (mRS), Modified Ashworth Scale (mAS), and neurophysiological parameters (MEP, EEG).

Timeline:

All outcome measures will be assessed at three time points: Baseline (T0), Post-treatment (T1, Week 3), and 1-month Follow-up (T2, Week 7).

Safety:

All adverse events, including rare severe events like seizures (<0.01%) and syncope, will be managed according to standard emergency protocols, and treatment will be discontinued if adverse effects persist or significant clinical weakness occurs. The study protocol is within established safety guidelines.

• Neuronavigation-Assisted rTMS for Stroke Hemiparesis (Device): Low-frequency (1 Hz) rTMS targeting the M1 "hotspot" contralateral to the lesion, delivered at 80% motor threshold (MT). Each session consists of 1,200 pulses (10 seconds ON, 1 second OFF, repeated 120 cycles). Treatment schedule: 1 session daily, 5 days/week, for 2 consecutive weeks (10 sessions total). Coil positioning is guided by a neuronavigational system using infrared camera and tracking balls.
• Standard Localization rTMS for Stroke Hemiparesis (Device): Low-frequency (1 Hz) rTMS targeting the M1 "hotspot" contralateral to the lesion, delivered at 80% MT. Each session consists of 1,200 pulses (10 seconds ON, 1 second OFF, repeated 120 cycles). Treatment schedule: 1 session daily, 5 days/week, for 2 consecutive weeks (10 sessions total). Coil positioning is performed using standard manual localization with cap positioning.

Primary outcomes

• Change in Fugl-Meyer Assessment (FMA) Score [Baseline (T0), Post-treatment (T1, 2 weeks), and 1 Month Post-treatment (T2)]: The FMA is a quantitative, reliable, and widely used stroke-specific assessment tool for measuring motor recovery. This scale ranges from 0 to 66 points, where a higher score indicates better motor function of the upper limb. The difference in FMA scores between the neuronavigation group and the standard localization group will be compared to evaluate the treatment efficacy.
• Deviation in Coil Positioning [Intra-session (recorded during each daily treatment session for 2 weeks) and Inter-session (change from baseline to 2 weeks)]: This measure quantifies the positional stability and accuracy of the rTMS coil placement. The neuronavigational system records positional coordinates before and after each session in the experimental group. The outcome will compare the intra-session (stability throughout a single treatment) and inter-session (change from baseline to 2 weeks) deviation in coil coordinates between the neuronavigation-guided group and the standard manual localization group.
• Time Required for Initial Hotspot Localization [Baseline (T0)]: This outcome measures the time (recorded in seconds or minutes) needed to accurately determine the M1 "hotspot" (the site eliciting the maximal motor-evoked potential (MEP)) at the start of the study. This comparison aims to quantify the efficiency difference between the neuronavigation-guided method and the standard manual localization method.

Sex: All, ages: 20 Years to 85 Years

Inclusion Criteria:

* First-ever ischemic or hemorrhagic stroke confirmed by imaging.
* Stroke causing unilateral upper limb weakness (MRC grade <=3)
* Stroke onset must be between 2 weeks and 6 months prior to enrollment (subacute phase).
* Age between 20 and 85 years old.
* Stable vital signs, clear consciousness, and no cognitive impairment.
* Able to cooperate with assessments and treatment.
* Written informed consent must be signed by the patient or a legal guardian.

Exclusion Criteria:

* Contraindications to TMS (e.g., metallic implants in head, pacemaker, cochlear implant).
* History of epilepsy or seizures.
* Pregnancy.
* Severe cognitive or communication disorders, or inability to give informed consent.
* Unstable medical conditions affecting participation.
* Use of certain medications, including benzodiazepines, antidepressants, muscle relaxants (baclofen, tizanidine), or ongoing botulinum toxin injections for post-stroke spasticity.
* Modified Rankin Scale (mRS) score >=5 .