Effect of Repetitive Transcranial Magnetic Stimulation (rTMS) on Serum Neurofilament Light Chain (sNfL) and its Correlation to Cognitive Function in Multiple Sclerosis
Ghaydaa A. Shehata, Mahmoud M. Hasan, Abd Elaziz Shokry, Hebatallah Abdellatif, Yassin M. Hassan, Ali Farrag Elhadad, Shymaa Salem, Abdelrahman N. AbdelalBackground
Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulatory technique that has emerged as a promising therapeutic intervention for various neurological disorders by modulating cortical excitability and neural plasticity. Multiple sclerosis (MS) is a chronic inflammatory demyelinating condition marked by central nervous system (CNS) lesions that can cause significant physical or cognitive disability, as well as neurological abnormalities. We now know that 40–70% of all MS patients have cognitive impairment that impairs their lives. Even in these so-called benign forms of the disease, 15 years after diagnosis, with an Expanded Disability Status Scale (EDSS) score of up to 3, cognitive abnormalities can be diagnosed in half of these patients.
Objective
To investigate whether high frequency (rTMS) can modify MS cognition assessed by clinical and serum Neurofilament Light Chain (sNfL).
Methods
Forty-five patients with relapsing-remitting multiple sclerosis (RRMS) were randomly allocated into three equal groups (n = 15 each): a 5-Hz rTMS group, an 18-Hz rTMS group, and a sham stimulation group. The treatment protocols were administered daily on five consecutive days weekly for 2 weeks over the vertex and left dorsolateral prefrontal cortex (lt. DLPFC). Cognitive performance was assessed using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS), comprising the Symbol Digit Modalities Test (SDMT), California Verbal Learning Test–Second Edition (CVLT-II), and Brief Visuospatial Memory Test–Revised (BVMT-R). Serum neurofilament light chain (sNfL) levels were measured as the secondary outcome.
Results
Repeated-measures ANOVA demonstrated significant time, group, and time-by-group interaction effects for sustained attention (SDMT), verbal learning and memory (CVLT-II), and visuospatial memory and learning (BVMT-R) (all
Conclusion
These findings suggest that repetitive transcranial magnetic stimulation (rTMS) applied over the left dorsolateral prefrontal cortex or vertex may provide short-term improvements in cognitive test performance, particularly in attention, verbal learning and memory, and visuospatial memory, with larger effects observed following Lt. DLPFC stimulation. However, these effects were transient and were not sustained at the 3-month follow-up, underscoring that any clinical benefit of the present protocol is short-lived rather than durable. By simultaneously evaluating cognitive outcomes alongside serum neurofilament light chain (sNfL), this integrated assessment of cognitive outcomes and sNfL adds a novel translational perspective to rTMS research in multiple sclerosis., this study offers a novel perspective on the possible biological correlates of cognitive change. The absence of significant changes in sNfL despite the observed cognitive changes is a hypothesis-generating observation, rather than direct mechanistic evidence, raising the hypothesis that these short-term cognitive changes may involve functional modulation of cortical networks rather than measurable changes in neuroaxonal injury. Given the exploratory nature and modest sample size of this trial, these findings support further investigation rather than establishing clinical efficacy.