High-frequency rTMS over the supplementary motor area improves freezing of gait in Parkinson's disease: a randomized controlled trial

Mi, Taomian; Garg, Saurabh; Ba, Fang; Liu, Aiping; Wu, Tao; Gao, Linlin; Dan, Xiaojuan; Chan, Piu; McKeown, Martin J.

doi:10.1016/j.parkreldis.2019.10.009

Cited by 48 publications

(79 citation statements)

References 28 publications

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“…Other stimulation site has also been explored. One recent RCT including 30 PD patients with FOG showed that 10 sessions of highfrequency (10 Hz) rTMS over the SMA had beneficial effects on FOG in PD patients [154]. This study also found that the beneficial effects could last at least 4 weeks after stimulation.…”

Section: Transcranial Magnetic Stimulation (Tms)supporting

confidence: 57%

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Freezing of gait in Parkinson’s disease: pathophysiology, risk factors and treatments

Gao

Tan

et al. 2020

Transl Neurodegener

123

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Background: Freezing of gait (FOG) is a common, disabling symptom of Parkinson's disease (PD), but the mechanisms and treatments of FOG remain great challenges for clinicians and researchers. The main focus of this review is to summarize the possible mechanisms underlying FOG, the risk factors for screening and predicting the onset of FOG, and the clinical trials involving various therapeutic strategies. In addition, the limitations and recommendations for future research design are also discussed. Main body: In the mechanism section, we briefly introduced the physiological process of gait control and hypotheses about the mechanism of FOG. In the risk factor section, gait disorders, PIGD phenotype, lower striatal DAT uptake were found to be independent risk factors of FOG with consistent evidence. In the treatment section, we summarized the clinical trials of pharmacological and non-pharmacological treatments. Despite the limited effectiveness of current medications for FOG, especially levodopa resistant FOG, there were some drugs that showed promise such as istradefylline and rasagiline. Non-pharmacological treatments encompass invasive brain and spinal cord stimulation, noninvasive repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) and vagus nerve stimulation (VNS), and physiotherapeutic approaches including cues and other training strategies. Several novel therapeutic strategies seem to be effective, such as rTMS over supplementary motor area (SMA), dual-site DBS, spinal cord stimulation (SCS) and VNS. Of physiotherapy, wearable cueing devices seem to be generally effective and promising.Conclusion: FOG model hypotheses are helpful for better understanding and characterizing FOG and they provide clues for further research exploration. Several risk factors of FOG have been identified, but need combinatorial optimization for predicting FOG more precisely. Although firm conclusions cannot be drawn on therapeutic efficacy, the literature suggested that some therapeutic strategies showed promise.

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Section: Transcranial Magnetic Stimulation (Tms)supporting

confidence: 57%

“…Of noninvasive brain stimulation, tDCS and rTMS have been examined for FOG treatment in PD. Pilot studies showed that SMA may be a moreappropriate target for rTMS in PD patients with FOG [154,155]. Besides, one recent study showed that VNS significantly improved FOG in 12 PD patients [152].…”

Section: Summary Of Non-pharmacological Treatments For Fogmentioning

confidence: 99%

Freezing of gait in Parkinson’s disease: pathophysiology, risk factors and treatments

Gao

Tan

et al. 2020

Transl Neurodegener

123

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“…The improvement of FOGQ score was used as the primary clinical outcome; with MDS-UPDRS III and a Timed Up-and-Go (TUG) test as secondary clinical outcomes. With a 4 week's follow-up, our results revealed a significantly decreased FOGQ score, significant improvements of MDS-UPDRS III and gait variables in the verum group; whereas no significant improvements were found in the sham group 8 .…”

Section: Introductionmentioning

confidence: 52%

“…In addition, patients in the verum and sham group had similar baseline characteristics. rTMS study: clinical efficiency A more detailed description of the clinical efficiency of rTMS can be found in our previous publication 8 . Briefly, the patients were assessed at baseline (T 0 ), after the 5th (T 1 ) and 10th (T 2 ) sessions, and then 2 weeks (T 3 ) and 4 weeks (T 4 ) after the last session.…”

Section: Participantsmentioning

confidence: 99%

Repetitive transcranial magnetic stimulation improves Parkinson’s freezing of gait via normalizing brain connectivity

Garg

et al. 2020

npj Parkinsons Dis.

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Robust, effective treatments for Parkinson's freezing of gait remain elusive. Our previous study revealed beneficial effects of highfrequency rTMS over the supplementary motor area. The present study aims to explore the neural mechanisms of rTMS treatments utilizing novel exploratory multivariate approaches. We first conducted a resting-state functional MRI study with a group of 40 Parkinson's disease patients with freezing of gait, 31 without freezing of gait, and 30 normal controls. A subset of 30 patients with freezing of gait (verum group: N = 20; sham group: N = 10) who participated the aforementioned rTMS study underwent another scan after the treatments. Using the baseline scans, the imaging biomarkers for freezing of gait and Parkinson's disease were developed by contrasting the connectivity profiles of patients with freezing of gait to those without freezing of gait and normal controls, respectively. These two biomarkers were then interrogated to assess the rTMS effects on connectivity patterns. Results showed that the freezing of gait biomarker was negatively correlated with Freezing of Gait Questionnaire score (r = −0.6723, p < 0.0001); while the Parkinson's disease biomarker was negatively correlated with MDS-UPDRS motor score (r = −0.7281, p < 0.0001). After the rTMS treatment, both the freezing of gait biomarker (0.326 ± 0.125 vs. 0.486 ± 0.193, p = 0.0071) and Parkinson's disease biomarker (0.313 ± 0.126 vs. 0.379 ± 0.155, p = 0.0378) were significantly improved in the verum group; whereas no significant biomarker changes were found in the sham group. Our findings indicate that high-frequency rTMS over the supplementary motor area confers the beneficial effect jointly through normalizing abnormal brain functional connectivity patterns specifically associated with freezing of gait, in addition to normalizing overall disrupted connectivity patterns seen in Parkinson's disease.

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“…Bereits 1996 wurden erste Versuche mit extrakraniellen elektromagnetischen Feldern durchgeführt [52], und 2019 wurde mit repetitiver transkranieller Magnetstimulation über dem supplementär-motorischen Kortex in einer randomisierten Studie ein positiver, sogar über einige Wochen anhaltender Effekt auf FOG gezeigt [53].…”

Section: Neuromodulationunclassified

Die Geschichte des ‚Freezing-of-gait‘ beim Parkinson-Syndrom – vom Phänomen zum Symptom

Klucken

Winkler

Krüger

et al. 2020

Fortschr Neurol Psychiatr

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ZusammenfassungIn der Übersichtsarbeit wird der Hintergrund des Phänomens Freezing-of-Gait (FOG) beim Parkinson-Syndrom beleuchtet. Die Charakterisierung des Phänomens als Symptom und die unterschiedlich definierten Subtypen werden diskutiert. Dabei stellen die unterschiedlichen Ausprägungsformen eine erhebliche Herausforderung an die alltägliche Behandlung und auch an die einheitliche Diagnostik bei klinischen Studien dar. Die bisherigen, standardisierten Erfassungsmethoden mittels Fragebögen und semistandardisierten klinischen Untersuchungen werden in Relevanz zur patientenspezifischen Versorgung dargestellt. Bei den derzeitigen Therapieformen spielen neben der Optimierung der dopaminergen Medikation gezielte medikamentöse Optionen bislang keine wesentliche Rolle, was aber auch an der Trennschärfe der standardisierten Diagnostik liegen kann. Dadurch ist beim variantenreichen Phänomen FOG auch die Evidenzlage der Tiefen Hirnstimulation eingeschränkt. Im Alltag können hingegen Physiotherapie und Cueing-Strategien sehr gute Erfolge erzielen, auch wenn die Studienlage bzgl. höchster Evidenzklasse eher gering ist. Die Entwicklungen der Technologie scheinen sowohl die diagnostische Trennschärfe als auch das individualisierte „Cueing“-Angebot zu revolutionieren. Aber auch hier fehlen noch ausreichend große Studien, die diese Diagnostik- und Therapieformen hinterlegen. Trotzdem ist davon auszugehen, dass vielen Patienten diese „neuen Tools“ gerne nutzen werden und der Behandlungsalltag für Arzt und Physiotherapeuten entsprechend belebt wird.

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High-frequency rTMS over the supplementary motor area improves freezing of gait in Parkinson's disease: a randomized controlled trial

Cited by 48 publications

References 28 publications

Freezing of gait in Parkinson’s disease: pathophysiology, risk factors and treatments

Freezing of gait in Parkinson’s disease: pathophysiology, risk factors and treatments

Repetitive transcranial magnetic stimulation improves Parkinson’s freezing of gait via normalizing brain connectivity

Die Geschichte des ‚Freezing-of-gait‘ beim Parkinson-Syndrom – vom Phänomen zum Symptom

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