MIAMI—For patients with Parkinson’s disease, a regime of transcranial magnetic stimulation (TMS) and aerobic exercise results in motor improvements that are sustained for one month, according to a study presented at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. Another study by the same researchers indicates that stimulation of two regions in the premotor associative cortex, compared with stimulation of one region, improves axial symptoms in Parkinson’s disease. Both studies suggest that TMS prolongs the cortical silent period.
TMS Prolonged Cortical Silent Period
Aerobic exercise improves the motor symptoms of Parkinson’s disease. A proposed mechanism for this improvement is the enhancement of brain-derived neurotrophic factor (BDNF) signaling or activity. TMS also improves motor symptoms of Parkinson’s disease, and rat studies indicate that it enhances BDNF-tropomyosin receptor kinase B (TrkB) signaling, which is a biomarker of plasticity.
Milton C. Biagioni, MD, Assistant Professor of Neurology at the Marlene and Paolo Fresco Institute for Parkinson’s and Movement Disorders at NYU Langone Health in New York, and colleagues studied differences in BDNF-TrkB signaling between 16 patients with Parkinson’s disease and five healthy controls. Levels of all TrkB signaling biomarkers were significantly higher in healthy controls than in patients with Parkinson’s disease.
Dr. Biagioni and colleagues also investigated the biologic effects, motor outcomes, and physiologic outcomes of repetitive TMS and aerobic exercise in patients with Parkinson’s disease in a randomized, double-blind trial. In this trial, 16 patients with Parkinson’s disease participated in daily 40-minute sessions of aerobic exercise. Participants were randomized 1:1 to receive high-frequency repetitive TMS or sham stimulation over the motor cortex. Patients exercised on a recumbent linear cross trainer.
Motor outcomes included the Unified Parkinson’s Disease Rating Scale (UPDRS) and Timed Up and Go (TUG) test. Neurophysiologic outcomes included the cortical silent period, motor threshold, and paired-associative stimulation (PAS-25). The researchers obtained peripheral blood lymphocytes from participants in the morning to measure BDNF activity. Outcomes were measured at baseline, two weeks after the intervention, and one month after the intervention.
Among patients with Parkinson’s disease, mean age was about 65. Mean disease duration was eight years, and mean UPDRS III score was 46.4. The researchers found no significant differences at baseline between patients randomized to TMS and those randomized to sham.
BDNF-TrkB signaling increased by 29.3% in the sham group and by 36.6% in the TMS group. Both increases were statistically significant, but the difference between groups was not significant. At one month, the cortical silent period was significantly prolonged after TMS, compared with sham. All patients had significant improvement in UPDRS III. Improvements in UPDRS III and TUG were sustained for one month in the TMS group.
Multifocal Stimulation Improved Axial Score
A previous study indicated that low-frequency repetitive TMS over the supplementary motor area (SMA) effectively improves motor symptoms in Parkinson’s disease. Like the SMA, the dorsal premotor cortex (PMd) is involved in motor planning and motor control. Researchers had not previously studied multifocal TMS over both targets, and Dr. Biagioni and colleagues decided to examine this technique.
They conducted a parallel, active-controlled, double-blind, randomized study of four weekly sessions of low-frequency repetitive TMS in 22 patients with Parkinson’s disease. The control group received TMS over the SMA and sham stimulation over the PMd. The experimental group received TMS over both areas. The study outcomes included all components of the UPDRS, as well as UPDRS III axial, tremor, rigidity, and bradykinesia scores. Dr. Biagioni and colleagues assessed patients in the on state at baseline and at four weeks after treatment.
Participants’ mean age was 65, and eight patients were female. Mean disease duration was approximately nine years, mean UPDRS total score was 53.1, and mean UPDRS III score was 35.9. The only significant difference between the control and experimental groups at baseline was Montreal Cognitive Assessment score, which was 24.2 in the control group and 26.4 in the experimental group.
Both interventions were well tolerated. After one month, UPDRS III decreased by 5.5 points in the control group and by 6.5 points in the experimental group. Both changes were statistically significant, but the difference between groups was not significant. The researchers found no difference between groups in total UPDRS and UPDRS III after one month. Axial score significantly decreased in the experimental group, compared with the control group, but the researchers found no significant differences between groups in rigidity, tremor, or bradykinesia scores. In addition, the cortical silent period was significantly prolonged in the experimental group, compared with the control group.
Chou YH, Hickey PT, Sundman M, et al. Effects of repetitive transcranial magnetic stimulation on motor symptoms in Parkinson disease: a systematic review and meta-analysis. JAMA Neurol. 2015;72(4):432-440.
Shirota Y, Ohtsu H, Hamada M, et al. Supplementary motor area stimulation for Parkinson disease: a randomized controlled study. Neurology. 2013;80(15):1400-1405.