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RESEARCH PAPER ANALYSIS

Intermittent theta-burst stimulation to enhance physical therapy in Parkinson's disease: The STEP-PD randomized trial.

In a double-blind randomized trial (STEP-PD), adding bilateral M1 intermittent theta-burst stimulation to a two-week intensive physical therapy program produced a modest but statistically significant acute improvement in OFF-state MDS-UPDRS III (Δ = -4.60, p = 0.034) with exploratory gains in gait…

PMID41926908
JournalNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
Publication Date2026-04-01
Ingested2026-04-28 08:58 PM
EXECUTIVE SUMMARY

What the AI sees

In a double-blind randomized trial (STEP-PD), adding bilateral M1 intermittent theta-burst stimulation to a two-week intensive physical therapy program produced a modest but statistically significant acute improvement in OFF-state MDS-UPDRS III (Δ = -4.60, p = 0.034) with exploratory gains in gait…

WHY IT MATTERS

Research significance

Provides a readily translatable, nonpharmacologic cortical-priming approach with objective EEG biomarkers that can enhance short-term rehabilitation outcomes in PD and serve as a platform for optimizing neuromodulation parameters and studying sustained clinical effects.

ABSTRACT

Source abstract

Physical therapy (PT) is commonly used to alleviate specific symptoms of Parkinson's disease (PD). Its efficacy may be enhanced by cortical priming, which aims to improve the brain's responsiveness to rehabilitation. This randomized, double-blind, sham-controlled trial-Stimulation to Enhance Physical Therapy in Parkinson's Disease (STEP-PD)-investigated whether combining PT with intermittent theta-burst stimulation (iTBS) applied over the primary motor cortex (M1-iTBS) could provide additional gains in motor function in patients with PD. Fifty participants with PD received PT combined with either bilateral M1-iTBS or sham-iTBS, twice daily, five days per week for two weeks. The primary outcome was the change in Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III) in the OFF-medication state, assessed at baseline and immediately post-intervention. Secondary outcomes included the Parkinson's Disease Questionnaire-39 (PDQ-39), and exploratory outcomes included clinical and instrumented assessments of gait and balance, as well as electroencephalography (EEG)-based measures of functional connectivity. Patients receiving PT combined with M1-iTBS showed greater acute improvement in OFF-state MDS-UPDRS III scores compared to those receiving sham stimulation (Δ = -4.60, p = 0.034). There were no significant differences in PDQ-39 scores. Exploratory analyses revealed improved gait stability, fewer falls, and reduced beta-band synchronization on resting-state EEG, suggesting that M1-iTBS may modulate motor networks to facilitate functional recovery. These findings suggest that combining PT with M1-iTBS has promise as an acute cortical priming approach to improve the short-term efficacy of PD rehabilitation, although further research is required to determine the sustainability of these effects.

SUPPORTING PAPER SET

32 more papers to review

Ranked by current scoring engine
1 The cGAS-STING-Glymphatic-gut Axis in Parkinson's disease: A proposed self-amplifying triad of Neuroinflammation and therapeutic opportunity. International immunopharmacology 91.0 2 Immunosenescence and Inflammaging as Drivers of Neurodegeneration: Cellular Mechanisms, Neuroimmune Crosstalk, and Therapeutic Implications. Cells 91.0 3 Flavonoids improve neurotransmitters for Parkinson's treatment: mechanism and therapeutic potential. Frontiers in pharmacology 88.0 4 Alpha-Lipoic Acid and Biotin in Neurodegenerative Diseases: Convergent Mechanistic Insights from Preclinical Models to Clinical Perspectives. Neurology international 78.0 5 The Gut Microbiota in Parkinson's Disease: Mechanistic Insights into Microbial-Host Interactions. Microorganisms 85.0 6 Linking inflammation, metabolic dysfunction, and neurodegeneration: a comprehensive review of TLR2 pathways in type 2 diabetes. Frontiers in clinical diabetes and healthcare 80.0 7 Neuroprotective effects of GLP-2 and a GLP-2/GIP dual receptor agonist in an MPTP-induced mouse model of Parkinson's disease. Peptides 86.0 8 TNF alpha unmasks enteric malate aspartate shuttle dysfunction bridging Parkinson disease and intestinal inflammation. Nature communications 91.5 9 Lipid Metabolism and Neurodegeneration: Mechanistic Insights and Therapeutic Targets. Ageing research reviews 82.0 10 Shared functional microbiome signatures in Parkinson's disease and constipation predominate irritable bowel syndrome despite taxonomic divergence. Brain, behavior, & immunity - health 80.0 11 Benzimidazole as a Versatile Scaffold for Developing Neurotherapeutics Against Neurodegenerative Diseases. ChemMedChem 74.0 12 Biomimicking neuromelanin reverses the gait deficits and dopaminergic neuronal loss in the Parkinson's disease. Colloids and surfaces. B, Biointerfaces 86.0 13 Neuroprotective roles of klotho: Molecular pathways and therapeutic implications for cognitive health in neurological and psychiatric diseases. Experimental physiology 84.0 14 Flavonoid Rutin Reduces Intestinal Inflammation in an Experimental Model of Parkinson's Disease. Neurotoxicity research 70.0 15 Nanostructured Lipid Carriers Enhance Brain Delivery and Antioxidant Efficacy of a Small-Molecule MAO B Inhibitor for Neurodegenerative Disease Therapy. Molecular pharmaceutics 78.0 16 Pathophysiological Role of the Gut Brain Axis in Parkinson's Disease: From Microbial Metabolites and Intestinal Permeability to Central Neuroinflammation. Current neurovascular research 86.0 17 Parkinson's Disease: From Metabolism to Genetics-A Comprehensive Review. Current issues in molecular biology 86.0 18 Navigating the cholesterol maze: Key insights on use of statins in neurodegenerative disorders. Neuroprotection (Chichester, England) 76.0 19 Integrative network pharmacology delineates dual GPCR and non-GPCR mechanisms of blended and individual Taikong Blue lavender and Pingyin rose essential oils in neurodegenerative and psychiatric disorders. Computers in biology and medicine 65.0 20 Models of neuroprotection in Parkinson's disease: Exploring cellular, molecular, and microenvironmental targets. Experimental neurology 78.0 21 Hyaluronic acid: emerging roles and biomaterial innovations in Alzheimer's and Parkinson's disease therapy. Frontiers in pharmacology 75.2 22 Molecular mechanisms underlying Parkinson's disease and role of phytochemicals, α-synuclein, sirtuins, and incretin mimetics in potential therapy. Frontiers in pharmacology 75.0 23 Lipid droplets in neurodegenerative diseases: pathological drivers and therapeutic vulnerabilities. Cell death discovery 82.0 24 Brain-gut-microbiota axis: a review on the bidirectional regulatory mechanisms between gut microbiota and brain and their disease interactions. Frontiers in microbiology 74.0 25 Long non-coding RNAs in neurodegenerative diseases - Molecular mechanisms, liquid biopsy biomarkers, and therapeutic targets: A review. Biomolecules & biomedicine 84.0 26 Neurosyphilis and Parkinsonism: Overlapping Pathophysiology and Emerging Therapeutic Insights. Current neurovascular research 76.0 27 Molecular biochemistry of soluble epoxide hydrolase in lipid mediator pathways and neuroinflammatory responses. The Journal of steroid biochemistry and molecular biology 82.0 28 Multifaceted role of CNPY2 beyond ER stress: Disease implications and therapeutic potential. Cell stress 83.3 29 Neuroprotective Role of Exercise-based Physiotherapy Combined with Pharmacological Agents in Parkinson's Disease. Central nervous system agents in medicinal chemistry 64.0 30 Distinct metabolomic and proteomic signatures in Parkinson's disease patients with REM sleep behavior disorder. Signal transduction and targeted therapy 84.0 31 HMGB1-mediated neuroinflammation: molecular mechanisms and emerging therapeutic approaches. Inflammopharmacology 78.0 32 Beyond acid-base dyshomeostasis: Dynamic instability of neuronal lysosomal pH as a pathogenic mechanism and therapeutic target in neurological diseases. Biochemical pharmacology 88.0
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