Multitarget transcranial magnetic theta-burst stimulation in the correction of cognitive impairment in patients with progressive multiple sclerosis

Cognitive impairment (CI) is a common symptom in multiple sclerosis (MS) that significantly impairs quality of life. Severe cognitive impairment with a multidomain phenotype is observed in progressive MS (PMS). Given the limitations of available therapeutic approaches to the treatment of CI in PMS, the investigation of transcranial magnetic stimulation (TMS) for its correction is relevant. Objective : To investigate the safety, tolerability and efficacy of multitarget navigated TMS in PMS with CI. Material and methods . A protocol for multitarget intermittent theta-burst stimulation (iTBS) of the left dorsolateral prefrontal and posterior parietal cortex was developed. Fifteen patients with PMS and CI were enrolled in the study: 8 patients received sham stimulation followed by active iTBS, and 7 patients received only active iTBS. Safety and tolerability were assessed by questionnaires, efficacy by neuropsychological testing and questionnaires on subjective CI and fatigue. Results . No serious adverse events (AEs) or discontinuation of TMS were observed. Mild AEs were recorded during 39.8% of sessions and within 24 hours after 23.3% of sessions, with no statistically significant differences between sham- and active iTBS. Verbal working and short-term memory (p=0.012 and p=0.049) as well as information processing speed (p=0.026), visuospatial perception (p=0.023), subjective CI (p=0.016) and fatigue (p=0.041) improved after the active protocol. Sham-iTBS had no significant effects. Significant differences between the effects of the sham and the active protocol were only observed for verbal working memory (p=0.043). Conclusion . Thus, this pilot study confirmed good safety and tolerability of the TMS protocol in PMS with CI. It was shown that there is a potential efficacy for verbal working and short-term memory, information processing speed, visuospatial perception, subjective CI and fatigue. The efficacy needs to be confirmed in further large studies.