This study evaluates transcranial direct current stimulation (tDCS) as a potential treatment for motor dysfunction in Progressive Supranuclear Palsy (PSP). PSP is a progressive neurodegenerative disorder characterized by vertical supranuclear gaze palsy, axial rigidity, postural instability, and bradykinesia. Despite extensive research, no disease-modifying treatments exist, making symptomatic management a critical area of investigation.
tDCS is a non-invasive brain stimulation technique that modulates cortical excitability through weak direct electrical currents delivered via electrodes placed on the scalp. The technique has shown promise in various neurological conditions including Parkinson's disease, stroke, and Alzheimer's disease.
- NCT Number: NCT07291687
- Status: Recruiting
- Study Type: Interventional
- Intervention: tDCS (Transcranial Direct Current Stimulation)
- Conditions: PSP (Progressive Supranuclear Palsy)
- Phase: Not applicable (Medical device study)
- Allocation: Randomized
tDCS works through several mechanisms:
- Modulation of cortical excitability: Anodal tDCS increases excitability, while cathodal tDCS decreases it
- Neuroplasticity enhancement: Promotes long-term potentiation-like changes in synaptic strength
- Network effects: Influences distributed brain networks beyond the stimulation site
- Neurotransmitter modulation: Affects dopamine, glutamate, and GABA signaling
In PSP, motor dysfunction manifests as:
- Bradykinesia: Slowness of voluntary movements
- Axial rigidity: Stiffness of trunk and neck muscles
- Postural instability: Impaired balance and increased fall risk
- Gait disturbance: Shuffling gait with reduced arm swing
The motor cortex and supplementary motor area are implicated in these deficits. tDCS targeting these regions may improve motor function by enhancing cortical excitability and promoting adaptive neuroplasticity.
Research on tDCS in PSP has yielded mixed results:
Positive findings:
- Language improvement with tDCS over dorsolateral prefrontal cortex (DLPFC)
- Improved walking speed with 4 mA tDCS
- Enhanced cognitive function in some studies
Negative findings:
- A 2024 randomized, double-blinded, sham-controlled trial found no effectiveness of prefrontal tDCS in PSP
This conflicting evidence highlights the need for additional well-designed trials to determine optimal stimulation parameters and target populations.
- Assess safety and tolerability of tDCS in PSP patients
- Evaluate effects on motor function (bradykinesia, gait, balance)
- Determine optimal stimulation parameters (intensity, duration, session number)
- Identify predictors of response (clinical phenotype, disease severity, genetic factors)
- Assess effects on quality of life and functional independence
- Randomized, double-blind, sham-controlled design
- Active tDCS vs. sham stimulation
- Parallel group assignment
- Current intensity: 1-2 mA (or 4 mA based on emerging evidence)
- Duration: 20-30 minutes per session
- Electrode placement: Motor cortex (M1) targeting primary motor and premotor areas
- Session schedule: Multiple sessions over 2-4 weeks
- Total sessions: 10-20 sessions
Motor assessments:
- Unified Parkinson's Disease Rating Scale (UPDRS) Part III
- PSP Rating Scale (PSPRS)
- Timed Up and Go (TUG) test
- 10-Meter Walk Test
- Berg Balance Scale
Cognitive assessments:
- MoCA (Montreal Cognitive Assessment)
- Trail Making Test
- Stroop Test
Quality of life:
- PDQ-39
- PSP Quality of Life Questionnaire
- Diagnosis of clinically definite or probable PSP
- Age 40-85 years
- Stable medication regimen for at least 4 weeks
- No contraindications to tDCS (see below)
- Ability to provide informed consent
- tDCS contraindications:
- Metal implants in the head
- Seizure history
- Active epilepsy
- Skin lesions at electrode sites
- Pacemaker or other electronic devices
- Significant psychiatric comorbidity
- Severe cognitive impairment preventing participation
- Orthopedic conditions limiting motor assessment
tDCS is generally well-tolerated with a favorable safety profile:
- Scalp tingling or itching at electrode sites
- Mild headache
- Transient skin redness
- Fatigue
- Skin irritation or burns (rare with proper protocols)
- Mood changes
- Sleep disturbances
tDCS offers several potential advantages as a therapeutic approach:
Unlike deep brain stimulation (DBS), tDCS does not require surgery, reducing risks and recovery time
tDCS can be combined with:
- Standard pharmacological treatments
- Physical therapy
- Cognitive rehabilitation
If proven effective, tDCS could enable:
- Home-based treatment protocols
- Cost-effective healthcare delivery
- Broader patient access
While tDCS is primarily symptomatic, some evidence suggests potential disease-modifying effects through neuroplasticity mechanisms