Controlled study of 50-Hz repetitive transcranial magnetic stimulation for the treatment of Parkinson disease

Abstract

Objective: To investigate the safety and efficacy of 50-Hz repetitive transcranial magnetic stimulation (rTMS) in the treatment of motor symptoms in Parkinson disease (PD).

Background: Progression of PD is characterized by the emergence of motor deficits that gradually respond less to dopaminergic therapy. rTMS has shown promising results in improving gait, a major cause of disability, and may provide a therapeutic alternative. Prior controlled studies suggest that an increase in stimulation frequency might enhance therapeutic efficacy.

Methods: In this randomized, double blind, sham-controlled study, the authors investigated the safety and efficacy of 50-Hz rTMS of the motor cortices in 8 sessions over 2 weeks. Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia, Unified Parkinson's Disease Rating Scale (UPDRS), and additional clinical, neurophysiological, and neuropsychological parameters. In addition, the safety of 50-Hz rTMS was tested with electromyography-electroencephalogram (EMG-EEG) monitoring during and after stimulation.

Results: The authors investigated 26 patients with mild to moderate PD: 13 received 50-Hz rTMS and 13 sham stimulation. The 50-Hz rTMS did not improve gait, bradykinesia, and global and motor UPDRS, but there appeared a short-lived "on"-state improvement in activities of daily living (UPDRS II). The 50-Hz rTMS lengthened the cortical silent period, but other neurophysiological and neuropsychological measures remained unchanged. EMG/EEG recorded no pathological increase of cortical excitability or epileptic activity. There were no adverse effects.

Conclusion: It appears that 50-Hz rTMS of the motor cortices is safe, but it fails to improve motor performance and functional status in PD. Prolonged stimulation or other techniques with rTMS might be more efficacious but need to be established in future research.

Figures

Figure 1

Flow diagram of patients with Parkinson’s disease (PD) enrolled in this therapeutic study.

Figure 2

A–D Gait and Sequential Hand and Arm Movement Time (A) Gait time before, 1 day and 1 month after the last intervention (mean ± standard error). The figure shows the time needed to walk 10 meters in the “on” and “off” state. Abscissa indicates the time of measurement. Ordinate indicates the gait time. The solid lines and diamonds indicate the 50 Hz rTMS (n=13) and the dashed lines and circles the sham group (n=13). Open symbols indicate the “off” (medication) condition and filled symbols indicate the “on” condition measurements. (B) Gait time before and after each intervention (mean ± standard error). The figure shows the time needed to walk 10 meters. Abscissa indicates the time of measurement; ordinate indicates the walking time. The solid lines and filled diamonds indicate the 50 Hz rTMS (n=13) and the dashed lines and open circles the sham group (n=13). At baseline, gait time did not differ between groups. (C) Sequential hand and arm movement test before, 1 day and 1 month after the last intervention (mean ± standard error). The figure shows the time needed to execute the sequential hand and arm movement test in the “on” and “off” state. Measurements for the left and right hands were pooled. Abscissa indicates the time of measurement. Ordinate indicates the execution time. The solid lines and diamonds indicate the 50 Hz rTMS (n=13) and the dashed lines and circles the sham group (n=13). Open symbols indicate the “off” (medication) condition and filled symbols indicate the “on” condition measurements. (D) Sequential hand and arm movement test before and after each intervention (mean ± standard error). The figure shows the time needed to execute the sequential hand and arm movement test. Measurements for the left and right hands were pooled. Abscissa indicates the time of measurement; ordinate indicates the execution time. The solid lines and filled diamonds indicate the 50 Hz rTMS (n=13) and the dashed lines and open circles the sham group (n=13). At baseline, sequential hand and arm movement time did not differ between groups.

Figure 3

Cortical Silent Period after 8 interventions Cortical Silent Period (CSP) 1 day after the last intervention (mean ± standard error). The figure shows the duration of CSP in seconds (abscissa) at the different stimulation intensities (in percentage of active motor threshold [ordinate]). The solid lines and diamonds indicate the 50 Hz rTMS (n=13) and the dashed lines and circles the sham group (n=13). Open symbols indicate the “off” (medication) condition and filled symbols indicate the “on” condition measurements. In this mixed model analysis, in which baseline was introduced as covariate and 90% intensity not included due to limited variance (therefore, not shown in the figure), the effect of 50 Hz rTMS on CSP (Treatment, p=0.049) is significant prior to correction for multiplicity.