Efficacy of repetitive transcranial magnetic stimulation on spasticity, disability, fatigue, cognition, quality of life and serum neurofilament light chain level in multiple sclerosis patients

Objective: Remyelination in multiple sclerosis (MS) is a very important process for the repair of inflammatory demyelinated lesions, adaptive plasticity has also been shown to be responsible for clinical improvement in MS. Transcranial magnetic stimulation (TMS) may have positive effects on both remyelination and neuroplasticity and also may change the course of MS. TMS is indicated with level B evidence in the treatment of spasticity in patients with MS and has begun to be tested in the treatment of other conditions that negatively affect quality of life. In line with this information, in this study, we aimed to evaluate the effect of intermittent theta burst stimulation (i-TBS), one of the repetitive TMS (rTMS) methods, on MS patients with spasticity in terms of spasticity, disability, quality of life, fatigue, cognition before and after application. We aimed to demonstrate the contribution of this method to neural plasticity and remyelination process by observing the change in serum neurofilament light chain level, which is a biomarker of axonal degeneration and progression. Materials and Methods: The study is a prospective, observational medical device clinical trial conducted at Ankara City Hospital between February 2023 and June 2023. 36 patients who applied to Ankara City Hospital Neurology MS outpatient clinics were included in the study. Physical examinations and scale evaluations of the patients (EDSS (Expanded Disability Status Scale), MAS (Modified Ashworth Scale), VAS (Visual Analog Scale-Pain), Timed 25-foot walk test, Barthel index, multiple sclerosis quality of life scale-54 (MSQOL-54), fatigue impact scale, fatigue severity scale and cognitive tests) at baseline were performed. Blood tests were taken to measure serum neurofilament light chain level. Then the patients were randomly divided into two equal groups and the first group was given intermittent theta burst stimulation therapy once a day, for a total of 10 sessions for 2 weeks. Blood tests and scale evaluations of the patients were performed 3 times in total, before stimulation (day 0) and twice after stimulation (1st month and 3rd month) in the i-TBS group. Neurofilament light chain levels were measured using the quantitative double antibody sandwich enzyme immunoassay technique. Control group was evaluated twice in total, on the 1st day and the 3rd month. SPSS 26.0 was used for the statistic analysis of the data and the statistical significance value was accepted as 'p <0.05'. Results: There was no statistically significant difference in gender distribution between the i-TBS and control groups (p = 0,289). There was no statistically significant difference between the groups in terms of age (p = 0,751) and disease duration (p = 0,976). As a result of the evaluations made before the application, in the 1st month after the application and in the 3rd month after the application, i-TBS, one of the rTMS methods, provided a significant improvement in the level of spasticity evaluated by the MAS score (p = 0,002), and there was a significant decrease in the VAS score, which rates pain p = 0,002). According to the results of the Timed 25-foot walk test, i-TBS provides benefits in terms of increased walking speed (p = 0,001). According to the results of the Barthel index evaluation, it has an effect in facilitating daily life activities (p = 0,005). According to the results of the California Verbal Learning Test (CVLT), it was observed that it improved verbal learning skills (p = 0,020) and visual-spatial memory according to the Brief Visuospatial Memory Test (BVMTR) test results (p = 0,006). In addition, no significant effect was observed on serum neurofilament level (p = 0.204). There is no statistically significant correlation between serum neurofilament level and disease duration (p = 0,139), age (p = 0,38), EDSS (p = 0,427), cognitive tests (SDMT p = 0,276, CVLT p = 0,497, BVMTR p = 0.309). Conclusion: Although transcranial magnetic stimulation therapy does not have a predictable positive effect on the course of the disease, it can have an effect on the restrictive symptoms that make the daily life of multiple sclerosis patients difficult and improve the quality of life. In addition, our study, in which we found improvement in cognitive functions, may be a guide for future research in this regard. Keywords: Multiple sclerosis, Transcranial magnetic stimulation, theta burst stimulation, neurofilament light chain