Highlights
- •Significant clinical improvements were only found after real rTMS stimulation.
- •The beneficial effects of rTMS could last at least 4 weeks after stimulation.
- •High-frequency rTMS over SMA may ultimately serve as an add-on therapy for FOG in PD.
Abstract
Introduction
Freezing of gait (FOG) contributes to falls in Parkinson's disease (PD), but robust,
effective treatments remain elusive. There is evidence indicating that the supplementary
motor area (SMA) plays an important role in the pathogenesis of FOG and may therefore
be a potential neuromodulation target. The present study explored the clinical efficacy
of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the SMA
on FOG in PD patients.
Methods
A group of 30 PD patients with FOG were enrolled in a randomized, double-blind, sham-controlled
trial. Patients were randomly allocated 2:1 to receive ten sessions of either real (N = 20) or sham (N = 10) 10 Hz rTMS over SMA. The patients were assessed at baseline (T0), after the 5th (T1) and 10th (T2) sessions, and then 2 weeks (T3) and 4 weeks (T4) after the last session. The primary clinical outcome was the Freezing of Gait Questionnaire
score (FOGQ), with the Movement Disorder Society-Unified Parkinson's Disease Rating
Scale motor scores (MDS-UPDRS III) and Timed Up and Go test as secondary clinical
outcomes. All the assessments were carried out at the “ON” state.
Results
With a four week's follow-up, there were significant interaction effects in the FOGQ
(effect of group*time, p = 0.04), MDS-UPDRS III (p = 0.02) and several gait variables
(total duration, p < 0.01; cadence, p = 0.04; turn duration, p = 0.01; and turn to
sit duration, p = 0.02). Post-hoc analyses revealed a significantly decreased FOGQ score at T2 and T4, and significant improvements of MDS-UPDRS III and gait variables at T1, T2, T3 and T4 in the rTMS group. No significant improvements were found in the sham group.
Conclusion
High-frequency rTMS over SMA may ultimately serve as an add-on therapy for alleviating
FOG in PD patients.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Parkinsonism & Related DisordersAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Freezing of gait: moving forward on a mysterious clinical phenomenon.Lancet Neurol. 2011; 10: 734-744
- Freezing of gait in PD: prospective assessment in the DATATOP cohort.Neurology. 2001; 56: 1712-1721
- Characterizing freezing of gait in Parkinson's disease: models of an episodic phenomenon.Movement disorders: official journal of the Movement Disorder Society. 2013; 28: 1509-1519
- Freezing of gait: a practical approach to management.Lancet Neurol. 2015; 14: 768-778
- Therapeutic application of repetitive transcranial magnetic stimulation: a review.Clin. Neurophysiol. : official journal of the International Federation of Clinical Neurophysiology. 2001; 112: 1367-1377
- Effects of repetitive transcranial magnetic stimulation on motor symptoms in Parkinson disease: a systematic review and meta-analysis.JAMA neurology. 2015; 72: 432-440
- Repetitive transcranial magnetic stimulation of the primary motor cortex in the treatment of motor signs in Parkinson's disease: a quantitative review of the literature.Movement disorders: official journal of the Movement Disorder Society. 2015; 30: 750-758
- The role of the prefrontal cortex in freezing of gait in parkinson’s disease: insights from a deep repetitive transcranial magnetic stimulation exploratory study.Exp. Brain Res. 2017; 235: 2463-2472
- Single session intermittent theta-burst stimulation on the left premotor cortex does not alleviate freezing of gait in Parkinson’s disease.Neurosci. Lett. 2016; 628: 1-9
- Effect of dual-mode and dual-site noninvasive brain stimulation on freezing of gait in patients with Parkinson disease.Arch. Phys. Med. Rehabil. 2017; 98: 1283-1290
- Efficacy of cumulative high-frequency rTMS on freezing of gait in Parkinson's disease.Restor. Neurol. Neurosci. 2015; 33: 521-530
- Repetitive transcranial stimulation for freezing of gait in Parkinson's disease.Movement disorders: official journal of the Movement Disorder Society. 2007; 22: 1518-1519
- Stimulation in supplementary motor area versus motor cortex for freezing of gait in Parkinson's disease.J. Clin. Neurol. 2018; 14: 320-326
- The supplementary motor area contributes to the timing of the anticipatory postural adjustment during step initiation in participants with and without Parkinson's disease.Neuroscience. 2009; 164: 877-885
- Differential neural activation patterns in patients with Parkinson's disease and freezing of gait in response to concurrent cognitive and motor load.PLoS One. 2013; 8e52602
- Functional reorganization of the locomotor network in Parkinson patients with freezing of gait.PLoS One. 2014; 9: e100291
- Knee trembling during freezing of gait represents multiple anticipatory postural adjustments.Exp. Neurol. 2009; 215: 334-341
- Gait-related cerebral alterations in patients with Parkinson's disease with freezing of gait.Brain. 2011; 134: 59-72
- High-frequency rTMS over the supplementary motor area for treatment of Parkinson's disease.Movement disorders: official journal of the Movement Disorder Society. 2008; 23: 1524-1531
- Increased corticospinal excitability after 5 Hz rTMS over the human supplementary motor area.J. Physiol. 2005; 562: 295-306
- Interhemispheric transmission of visuomotor information for motor implementation.Cerebr. Cortex (New York, N.Y. : 1991). 2005; 15: 1025-1036
- The relevance of clinical balance assessment tools to differentiate balance deficits.Eur. J. Phys. Rehabil. Med. 2010; 46: 239-248
- Stepped Care to Optimize Pain care Effectiveness (SCOPE) trial study design and sample characteristics.Contemp. Clin. Trials. 2013; 34: 270-281
- Analyzing repeated measurements using mixed models.Jama. 2016; 315: 407-408
- Supplementary motor area stimulation for Parkinson disease: a randomized controlled study.Neurology. 2013; : 1400-1405
- Placebo-controlled study of rTMS for the treatment of Parkinson's disease.Movement disorders: official journal of the Movement Disorder Society. 2006; 21: 325-331
- Subthalamic nucleus stimulation and dysarthria in Parkinson's disease: a PET study.Brain. 2004; 127: 602-615
- A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition.Clin. Neurophysiol. : official journal of the International Federation of Clinical Neurophysiology. 2006; 117: 2584-2596
- Pharmacological Treatment in Parkinson's Disease: Effects on Gait.Parkinsonism & related disorders, 2016
- Impaired cognitive control in Parkinson's disease patients with freezing of gait in response to cognitive load.J. Neural Transm. 2015; 122: 653-660
- Ability to modulate walking cadence remains intact in Parkinson's disease.J. Neurol. Neurosurg. Psychiatry. 1994; 57: 1532-1534
Article info
Publication history
Published online: October 11, 2019
Accepted:
October 10,
2019
Received in revised form:
October 4,
2019
Received:
May 9,
2019
Identification
Copyright
© 2019 Elsevier Ltd. All rights reserved.
