Effectiveness of Transcranial Magnetic Stimulation on Dysphagia in Patients With Parkinson's Disease: A Randomized Double-Blind Study
Phase: NA
Conditions: Dysphagia, Parkinson&#39;s Disease (PD)
Sponsor: Ege University

STUDY PROTOCOL AND STATISTICAL ANALYSIS 
 
 
Official Title: Effectiveness of Transcranial Magnetic Stimulation on Dysphagia in Patients 
with Parkinson's Disease: A Randomized Double-Blind Study 
Unique Protocol Id: E-70198063 
Date: 22.10.2025 
 
Our study included patients aged 40-75 years with a diagnosis of Parkinson's disease who 
were followed up at the Physical Medicine and Rehabilitation and Neurology outpatient 
clinics and who experienced dysphagia symptoms. Inclusion criteria included being followed 
up with a diagnosis of Parkinson's disease, moderate to severe Parkinson's disease (Hoehn-
Yahr 2-4), patients describing dysphagia symptoms, and being able to give informed consent. 
Exclusion criteria included intracranial metallic devices, cardiac pacemakers, history of 
seizures, antipsychotic use, diagnosis of depression, diagnosis of dementia, findings of 
additional neurological disease (intracranial lesion on imaging, hydrocephalus, positive 
Babinski sign, cerebellar signs), and normal FEES evaluation.  
A total of 129 patients followed up with a diagnosis of Parkinson's disease from the Physical 
Medicine and Rehabilitation and Neurology outpatient clinics were screened based on their 
files. Forty-one patients who met the inclusion criteria were interviewed. Six patients declined 
to participate in the study. Six patients experiencing dysphagia symptoms had normal FEES 
results. The remaining 29 patients were included in the study. After randomization, there were 
14 participants in the 5 Hz group and 15 participants in the 10 Hz group. During the treatment 
process, one patient from the 5 Hz group and two patients from the 10 Hz group withdrew 
from the study for personal reasons. Thirteen patients from each group participated in the 
post-treatment and 9-month follow-up evaluations. The relevant study flow chart is shown in 
Figure 1. 
Patient files were scanned through the hospital system, and patients who met the inclusion 
criteria for the study were contacted by telephone. During this conversation, patients were 
informed about the content, purpose, duration, and possible complications of the study. 
Patients who agreed to participate in the study were invited for an examination. During this 
examination, patients were assessed for the presence of exclusion criteria. For patients 
deemed suitable for participation, the swallowing assessment form, FOIS, FSS, and EAT-10 
test were completed. This was followed by a flexible endoscopic swallowing evaluation 
(FEES). During this evaluation, the YALE-2016 valeric residue scale, YALE-2016 piriform 
sinus residue scale, and penetration aspiration scale were scored. Participants were then 
assigned to one of two treatment groups. 
Randomization was performed using a computer program. Treatments were administered at 5 
Hz to one group and 10 Hz to the other group. Treatments consisted of a total of 10 sessions 
over two weeks, applied bilaterally to the pharyngeal and mylohyoid cortex by another 
researcher. Neither the researchers performing the assessments nor the patients were aware of 

the treatment group. The TMS device used in our clinic was the Magstim Rapid 2 (Magstim 
Co Ltd, Spring Gardens, Whitland, UK), and a butterfly coil (D70) was used for stimulation. 
All treatment parameters except frequency were kept the same in both treatment groups. 
rTMS treatment was administered with a pulse duration of 10 seconds, an interval of 25 
seconds, a total of 2000 pulses, and a stimulation intensity of 90% of the RMT of the first 
dorsal interosseous muscle of the hand. The current literature was reviewed when determining 
the treatment stimulation point. Studies conducted with stroke patients showed that 4-6 cm 
lateral and 2-4 cm anterior to the vertex were used for mylohyoid cortex stimulation. (17–20) 
The study referenced by all these studies is the one conducted by Khedr et al., in which the 
cortical topography of the swallowing muscles was mapped. (21) In our study, the vertex 
point was determined according to the international 10–20 method. Subsequently, based on 
the existing literature, 6 cm lateral and 3 cm anterior to the vertex point was determined as the 
mylohyoid and pharyngeal cortex stimulation point. Both groups were given cervical 
strengthening, shaker, massako exercises, and triflo breathing exercises as home exercises. 
After 10 sessions of rTMS treatment, the patients underwent a second evaluation, and the 
scores from the first evaluation were used.  
After rTMS treatment, patients were asked to continue swallowing exercises. They were 
called for a follow-up evaluation at 9 months. The same evaluations performed at the first and 
second visits were also performed at the third visit.  
 
G-Power software was used to calculate the sample size. According to the ANOVA analysis, 
the significance value was p<0.05; the effect size was 0.30, and the minimum sample size was 
calculated as 26 at a 95% confidence interval.  
The statistical analysis of the study was performed using IBM SPSS Statistics version 27.0 
and R analysis version 4.5.0. Descriptive statistical methods were used to examine 
demographic data. The normality of data distribution was assessed using the Shapiro-Wilk 
test. Since the data were found to be non-normally distributed, non-parametric tests were 
used.  
The “Cochran test” and “Brunner Langer test” were used to evaluate the time-dependent 
distribution of categorical data within groups, and the “Dunn Bonferroni test” was used for 
pairwise comparisons of significant data. The “Chi-square test” was used for the intergroup 
evaluation of categorical data. The Friedman test was used to evaluate the time-dependent 
change in numerical data within groups, and the Mann-Whitney U test was used for the 
intergroup evaluation. The correlation of pre-treatment parameters was evaluated using 
Spearman correlation analysis. 
The statistical significance level was set at p<0.05.