Clinical and Neurophysiological Effects of the Therapeutic Combination of High-Frequency Rhythmic Transcranial Magnetic Stimulation of the Motor and Frontal Cortex in Parkinson’s Disease

Objective. To run a parallel placebo-controlled trial to assess the effects of navigated combined high-frequency rhythmic transcranial magnetic stimulation (rTMS) of the primary motor (bilateral) and left dorsolateral prefrontal cortex on the clinical dynamics of the symptoms of Parkinson’s disease (PD). Materials and methods. A total of 46 patients took part in the trial and were randomized to active (n = 23) and placebo (n = 23) rTMS. Navigated therapeutic and placebo rTMS were performed for areas of the primary motor and left dorsolateral prefrontal cortex at a frequency of 10 Hz (20 daily sessions for three weeks). Changes in clinical symptoms were assessed on the MDS-UPDRS (parts I–IV) before sessions, immediately after 20 sessions, and 4–6 weeks after courses of rTMS. Nonmotor and mental symptoms were evaluated on the Hamilton depression scale (HDRS-17), the Beck scale (BDI-II), the depression, anxiety, and stress scale (DASS-21), and the mini mental state examination (MMSE). Results. Statistically signifi cant therapeutic effects were obtained with rTMS as compared with placebo, with greater reductions in total scores on the MDS-UPDRS (parts I–IV), the severity of nonmotor (part I)and motor (Part III, with greater therapeutic effects for rigidity, bradykinesia, and postural instability) signs, as well as the severity of motor complications of dopamine replacement therapy (part IV). The effects of rTMS on motor symptoms persisted at four weeks after completion of stimulation courses. It is also important to note that the signifi cant improvements in the rTMS and placebo groups were similar in terms of the magnitudes of reductions in the severity of daily motor symptoms (part II of the MDS-UPDRS) and increases in the total scores on the MMSE, HDRS, BDI-II, and DASS-21. Conclusions. Combined high-frequency rTMS of two areas of the cerebral cortex – the motor (bilaterally) and the left dorsolateral prefrontal – had positive therapeutic effects on the motor and affective symptoms of PD which were signifi cantly greater than obtained using placebo stimulation.