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Repetitive Transcranial Magnetic Stimulation Shows Effectiveness in Treating Excessive Daytime Sleepiness in Parkinson Disease

In comparison to nonresponders, those in the active treatment group who did respond well exhibited longer disease duration and lower baseline levodopa equivalent dose.

According to recently published findings from a sham-controlled, parallel study, low frequency repetitive transcranial magnetic stimulation (rTMS) over right dorsolateral prefrontal cortex (DLPFC) significantly improved symptoms of excessive daytime sleepiness (EDS) in patients with Parkinson disease (PD).1

A total of 25 individuals were randomly assigned to active treatment of 1 Hz rTMS (n = 15) for 10 consecutive days or sham (n = 10), with changes on Epworth Sleepiness Scale (ESS) as the primary outcome. All told, after 10 days, significant improvements of 15.65% (±17.18) were observed in the active treatment group (P <.05). These continued to be observed at the second follow-up, 30 days later (ESS improvement , 16.72%; ±14.33; P <.05).

"To be noted, as an adjunctive therapeutic strategy, current rTMS study was aimed to alleviate EDS in PD but not to completely remove or cure the symptoms,” senior investigator Chun-Feng Liu, MD, PhD, director, Soochow University, and colleagues, wrote. “Further studies with large sample size, refined stimulation mode (stimulation site or session) and detailed evaluation endpoint are needed to confirm and better display the results of rTMS effect."

To date, only 2 studies had reported on the improvement of EDS with high frequency rTMS over DLPFC in patients with narcolepsy, while its effects in PD population remained unknown. Previous research conducted by Liu et al had suggested that low frequency rTMS over right DLPFC benefited general sleep quality of PD. Considering that DLPFC is involved in functions of regulating emotion, execution, as well as sleep, investigators hypothesized that the pathological change of DLPFC in patients with PD may be related to nonmotor symptoms such as depression, cognitive deficits, and sleep disturbance.

Between the active and sham groups, there were no significant differences on demographics. All participants completed the follow-ups, and no adverse events (AEs) were noted during the study. While patients on active treatment showed significant decreases in ESS score, no significant changes were observed in the sham group. For the active group, all scales that evaluated motor and other nonmotor symptoms showed significant improvement at first follow-up.

Aside from Unified Parkinson Disease Rating Scale (UPDRS) total score and UPDRS-III, the therapeutic effects from rTMS lasted for 1 month. In a correction analysis, the percentage of change of ESS score in the active group was positively related to the baseline duration of disease (first follow-up, r = .788; second follow-up, r = .571; P <.05 for both).

A deeper look at ESS change in the active rTMS group showed that the percentage change of Montreal Cognitive Assessment (MoCA) score of responders on ESS was significantly higher than nonresponders at the 2 follow-ups (P <.05). Meanwhile, the responsive group had significantly longer duration of disease and higher baseline score of UPDRS and UPRDS-III than nonresponders at the first follow-up, and significantly lower levodopa equivalent dose (LED) than the nonresponsive group at second follow-up (P <.05).

Results also showed an inverse correlation between the percent change of ESS score in the responsive group and change of MoCA score at first follow-up (r = –0.721; P <.05) but not at second follow-up (r = –0.188; P >.05). Although the percentage change of ESS score in the responsive group showed a trend of positive correlation with the duration of disease at both follow-ups, the result was not statistically significant (first follow-up, r = .600; second follow-up, r = .471; P >.05).

The study investigators wrote, "According to our results, the improvement of symptoms of EDS may be associated with longer duration of disease and less LED, but independent of mood. First of all, we believe that the improvement of EDS in patients with longer duration of disease may benefit from the improvement of more severe nonmotor symptoms according to our statistical analysis, as the impact of nonmotor symptoms on PD related EDS could be aggravated with the increase of duration of disease."

REFERENCE
1. Zhang X, Zhuang S, Wu J, et al. Effects of repetitive transcranial magnetic stimulation over right dorsolateral prefrontal cortex on excessive daytime sleepiness in patients with Parkinson disease. Sleep Med. 2022;100:133-138. doi:10.1016/j.sleep.2022.08.003.