Transcranial Pulse Stimulation (TPS) study in Parkinson’s disease

Retrospective clinical data analysis on neuromodulation with TPS as an add-on therapy in patients with Parkinson’s disease

Transcranial Pulse Stimulation (TPS) is a non-invasive method of brain stimulation that is the focus of current scientific research, particularly due to its already well-documented effectiveness in the treatment of Alzheimer’s disease. Numerous universities and research institutions around the world are dedicated to investigating this technology and its potential applications for other neurological indications.

Pilot projects and clinical observational studies conducted over a period of more than twelve years have also provided promising data for Parkinson’s disease.

In a retrospective analysis by the Medical University of Vienna, initial results now indicate that TPS can further improve motor symptoms in Parkinson’s patients who are already receiving optimized standard therapy. This study not only confirms the therapeutic efficacy of TPS, but also underlines its safety, as no clinically relevant side effects were found.

Furthermore, the research takes into account the importance of placebo response, a key aspect in non-invasive brain stimulation studies, and thus provides a comprehensive contribution to the understanding and evaluation of TPS in the context of Parkinson’s treatment.

Evaluation of the safety and clinical efficacy of Transcranial Pulse Stimulation (TPS) in Parkinson’s disease

In the study conducted by the Medical University of Vienna, Transcranial Pulse Stimulation (TPS) in Parkinson’s patients was the focus of an open, retrospective study. The central research questions aimed to determine whether TPS is both safe and feasible in a wide range of Parkinson’s patients typically encountered in clinical practice. In addition, it was investigated whether there is evidence of clinical effects based on the analysis of clinical scores.

The primary outcome of the study was the change in the Unified Parkinson’s Disease Rating Scale Part III (UPDRS-III), which specifically assesses motor function in Parkinson’s patients. The assessment was carried out after completion of TPS treatment compared to the baseline values before treatment. This methodological approach allowed the researchers to draw direct conclusions about the effectiveness of TPS in improving motor symptoms in Parkinson’s patients while evaluating the safety and feasibility of the method in a real-world clinical context.

Patient population and TPS treatment methodology

The study included 20 Parkinson’s patients (15 men, 5 women; mean age: 67.6 years; disease duration: 3 – 148 months), diagnosed by external neurologists. This group of patients received ten TPS sessions over two weeks as a treatment trial. Inclusion criteria were a treatment request, clinical stability, a UPDRS-III assessment before and after therapy by external neurologists and written informed consent. The selection reflected a broad spectrum of Parkinson’s subtypes and comorbidities, which allowed the investigation of TPS safety and efficacy in a clinically realistic setting.

This group received ten TPS sessions over a two-week period upon request as an add-on therapy. Inclusion criteria included clinical stability, prior and subsequent UPDRS-III evaluation by external neurologists, and informed consent in addition to treatment request. The diversity of subtypes and comorbidities among the patients allows for a comprehensive analysis of TPS in terms of safety and potential clinical effects.

Prior to treatment initiation, high-resolution MRI scans were performed for exclusion diagnosis, assessment of brain morphology and TPS navigation. Each patient also received a functional neurological examination to assess their clinical condition. Target areas for TPS stimulation, such as the primary sensorimotor area and other relevant motor areas, were determined based on the MRI images.

Depending on the symptoms, additional areas, such as the left dorsolateral prefrontal cortex in depression, were included. As standard, 4000 ultrashort ultrasound pressure pulses (energy flux density = 0.25 mJ/mm², pulse repetition rate = 4 Hz) were used in each session. Real-time tracking enabled precise targeting and even pulse distribution.

Patient safety and adverse events (AEs)

AEs were monitored during the 2-week TPS therapy. Patients reported any AEs that occurred after each session and rated pressure and pain experiences using visual analog scales (VAS; 0 = none and 10 = very severe pressure/pain). 13 patients (65%) reported mild AEs such as fatigue and headache, which resolved within one day. VAS results predominantly showed no pressure experience (91.5% VAS 0).

Clinical evaluation and results

Clinical assessments were performed within 4 weeks before and after the TPS sessions, on average 14 days before and 13 days after therapy. Independent neurologists performed assessments in the “ON” state, using UPDRS-III to assess motor changes. Statistical analyses were performed using IBM SPSS Statistics (version 28) statistical analyses, with a paired t-test showing significant effects at p < 0.05.

Motor improvements significant

UPDRS-III scores improved significantly after TPS (before: 16.70 ± 8.85, after: 12.95 ± 8.55; p < 0.001). Seven patients improved by at least five points, with no deterioration in any patient.

The results of TPS therapy with regard to the placebo effect

However, the results presented were not compared with a control group that received a sham treatment. Therefore, the observed therapy successes could also include placebo effects, as described in the clinical NIBS literature on various non-invasive brain stimulations. Various studies suggest that placebo treatments may stimulate dopamine release in the dorsal striatum, which is related to the placebo-induced improvements in Parkinson’s symptoms. Similarly, the expectation of symptom improvement from placebo administration may be linked to increased dopamine release in the ventral striatum and activation of the reward system.

According to the authors, a placebo effect in the study would have been possible for several reasons: Non-pharmacological interventions often generate stronger placebo responses, these increase with the intensity and duration of treatment, and the demand for TPS signals high expectations.

However, the clear pattern and frequency of motor improvements (19 out of 20 patients improved) make exclusive placebo effects unlikely. From previous TPS studies that included sham controls and independent neurophysiological data (EEG and fMRI), there is clear evidence of TPS modulation of somatosensory evoked potentials, long-term neuroplastic changes and long-term improvement in cognitive function even in Alzheimer’s dementia and depression. These findings, along with other clinical data, emphasize the potential of Transcranial Pulse Stimulation (TPS) to emerge as a novel complementary neuromodulation therapy.

TPS: A new horizon in the treatment of neurodegenerative diseases

The scientists also conclude that Transcranial Pulse Stimulation (TPS) is a promising new brain stimulation technique for the treatment of Parkinson’s disease with TPS. The results presented support and expand the understanding of the safety and efficacy profile of TPS in the treatment of neurodegenerative diseases such as Parkinson’s disease.

Prospective, sham-controlled studies with larger sample sizes are needed to further expand knowledge of this approach, including long-term effects. However, the findings of this retrospective analysis provide a strong argument to illustrate the value of Transcranial Pulse Stimulation (TPS) as a new complementary therapy for PD as well and to further explore it here.

The study was published in the Journal of Neurology:

Further studies on Transcranial Pulse Stimulation (TPS) shock wave therapy for various indications in neurology and psychiatry can be found here:

Transcranial Pulse Stimulation (TPS) – Studies