Current studies on Transcranial Pulse Stimulation (TPS)
Dr. Gilson Shinzato, University of São Paulo, in an interview on new TPS studies
Transcranial Pulse Stimulation (TPS) is becoming increasingly important worldwide in the treatment of Alzheimer’s dementia and other neurodegenerative and neurophysiological diseases. In South America, the Institute of Rehabilitation Medicine (IMREA) at the University of São Paulo in Brazil is a leader in this field. The institute is currently conducting a double-blind, randomized, placebo-controlled study on the effectiveness of TPS in Alzheimer’s dementia.
The study entitled “Non-invasive Brain Stimulation by Transcranial Pulse Stimulation as a Coadjunctive Treatment in Alzheimer’s Disease” (ClinicalTrials.gov ID: NCT05762926), funded by the University of São Paulo General Hospital, is led by Gilson Tanaka Shinzato, MD, and Prof. Linamara Rizzo Battistella in collaboration with Prof. Orestes Forlenza, a leading Alzheimer’s researcher at the Institute of Psychiatry of the University of São Paulo.
We spoke to Gilson Shinzato about the benefits and opportunities of the TPS brain stimulation method.
Alzheimer Science (AS): “Dr. Shinzato, given the rapidly growing number of dementia cases in South America, especially in Brazil, how is Alzheimer’s dementia and other neurodegenerative diseases being dealt with in your country?”
Gilson Shinzato (GS): “Alzheimer’s disease is a significant challenge in Brazil. I would like to refer to a study by Piovesan et al. (2023) 1 , which recorded around 188,811 Alzheimer’s-related deaths from 2010 to 2020 and an 88 percent increase in hospitalizations for Alzheimer’s, which now even exceeds cerebrovascular and ischemic heart disease. In 2020, Alzheimer’s-related deaths increased by three percent, probably also due to COVID-19. The study shows the significantly increasing burden of Alzheimer’s in Brazil, with rising mortality, hospitalization rates and costs. Transcranial pulse stimulation offers a great opportunity as an effective therapy for Alzheimer’s and other diseases.”
Alzheimer Science (AS): “You have many years of experience in shockwave medicine and have followed the development of transcranial pulse stimulation over the last years. What were the decisive factors for you to bring TPS to your university?”
Gilson Shinzato (GS): “My first contact with the method, which was still called transcranial extracorporeal shock wave treatment (TESWT) at the time, was in 2014 when I heard the inspiring presentations by Henning Lohse-Busch, MD, at the ISMST World Congress in Milan. He presented remarkable improvements in patients with severe traumatic brain injury using TESWT 2. Inspired by these advances, I informed Professor Linamara Rizzo Battistella at the University of São Paulo, who then invited Dr. Lohse-Busch to a national congress. There he expanded our knowledge of TESWT in dementia and stroke patients. We followed the development of transcranial pulse stimulation closely and carried out experimental studies with shock waves on animal models, which confirmed the clinical data from the Europeans. As a result, we wanted to start our own national studies immediately.”
Alzheimer Science (AS): “But of course you were also affected by the unexpected restrictions of the coronavirus pandemic?”
Gilson Shinzato (GS): “Yes, unfortunately this project was slowed down by the outbreak of COVID-19. We would have been much further along otherwise. In 2023, we finally started an exploratory open-label study with 10 patients, which showed remarkable improvements. The results were submitted for publication, and we started the second phase of the RCT to treat 40 more patients.”
Alzheimer Science (AS): “The first patient you treated with TPS was your own mother, who had MCI (Mild Cognitive Impairment). Can you tell us how the TPS treatment affected her quality of life?”
“My mother, who had clinical signs of MCI (mild cognitive impairment, or pre-dementia), improved, and has been living independently for nine years, thanks to TPS.”
Gilson Shinzato, M.D.
Gilson Shinzato (GS): “In 2015, my mother, a former teacher and daughter of Japanese immigrants, began to show memory lapses at the age of 76. Advised by Dr. Lohse-Busch we started TPS treatment and regular booster sessions, which led to a remarkable normalization of her memory and cognitive functions, which have now been stable for nine years! Today, at the age of 85, she leads an independent life thanks to TPS.”
Alzheimer Science (AS): “You were then able to repeat this success over time at your university as part of your treatment and research work. How many patients have been treated with TPS so far?”
Gilson Shinzato (GS): “We treated 72 patients with various neurodegenerative diseases, strokes and Long-COVID and achieved really surprising results, which are not yet sufficiently documented for publication. I would like to mention a few impressive examples here:
- A 75-year-old pediatrician with Alzheimer’s disease and aphasia who was able to speak fluently and use digital devices after TPS treatment. Despite multiple setbacks, including COVID-related cognitive loss, TPS led to amazing recoveries over a year.
- An 88-year-old former piano teacher with Lewy body dementia, who suffered from severe hallucinations, experienced significant improvement after TPS therapy. Her cognitive functions stabilized over four years, which helped her to maintain her independence.
- After an ischemic stroke and years of aphasia, a 76-year-old priest regained his ability to speak through TPS and has since been able to hold religious ceremonies again.
- A 98-year-old former dressmaking and sewing teacher with advanced Alzheimer’s began speaking and interacting again after a series of TPS sessions, remembered her own and her daughter’s name, and became more autonomous in self-care.
- A 39-year-old woman with right-sided hemianesthesia, left-sided trigeminal pain and mood instability following a stroke responded positively to TPS, leading to a significant improvement in her symptoms and allowing her to go about her day normally, apart from persistent nystagmus.
These cases clearly illustrate the potential of TPS therapy in treating and improving the quality of life of our patients.”
Alzheimer Science (AS): “As a result, your university has decided to conduct an RCT- study on TPS in Alzheimer’s dementia. What is the status of this?”
Gilson Shinzato (GS): “Despite the enormous prevalence of Alzheimer’s disease, it is not easy to recruit patients for a clinical trial. The reason for this is the offshoots of the corona pandemic, but it is also the family dynamics and the degree of dependency of these patients, unfortunately also the poor results of previous pharmacological strategies and the lack of treatment options, which reduce the hopes of families and the credibility of new methods. Fortunately, our collaboration with the Alzheimer’s research laboratory of the IPq (Institute of Psychiatry of the Hospital das Clínicas of the University of São Paulo) is helping us with recruitment, and we hope to soon reach the number of subjects planned for the study.”
Alzheimer Science (AS): “There is a great call for placebo-controlled studies on TPS. How do you rate the placebo effect?”
“We assume, that the long-lasting improvements and effects of TPS are certainly far superior to the placebo effect, even in advanced diseases.”
Gilson Shinzato, M.D.
Gilson Shinzato (GS): “The placebo effect is not only psychological, but also causes real physiological changes and is important in any treatment method, which is why placebo-controlled studies are needed to measure the actual effect of the intervention. Although we know that a placebo effect may also be possible with TPS, we believe that the long-lasting improvements and effects are certainly far superior to the placebo effect even in advanced disease. We are now conducting the RCT to test this hypothesis, measure the actual impact of the placebo effect in TPS and publish the results as soon as possible”
Alzheimer Science (AS): “Your study will also help to further prove the efficacy, benefits and safety of Transcranial Pulse Stimulation (TPS) in Alzheimer’s dementia. Will you undertake further research on other indications after this study is completed?”
Gilson Shinzato (GS): “Of course! We are already planning further studies on TPS for Parkinson’s, stroke and traumatic brain injury as well as Long-COVID. There are many patients with these conditions in our rehabilitation hospital and the implementation of these studies will support the further development of TPS research and treatment protocols.”
Alzheimer Science (AS): “How important is TPS today or will be in the near future for the treatment of affected patients and how should TPS be integrated into multimodal therapy concepts?”
Gilson Shinzato (GS): “We give transcranial pulse stimulation a very high priority in therapy and rehabilitation, also in the context of multimodal treatment options. Finally, it is also quite remarkable and relevant that modern pharmacology is demonstrably supported by TPS through the presumed opening of the blood-brain barrier (BBB), as we know from the research work of Prof. Dr. Dr. Ulrich Sprick from Alexius-Josef Hospital in Neuss/Germany. In addition to TPS, we also have a line of research at our facility with TMS and tDCS, and we believe that the combination of multimodal non-invasive brain stimulation techniques (NIBS) will soon be commonplace. But it is TPS in particular that should be available to patients, as it also reaches deep brain areas precisely and only a few treatments are needed to significantly improve the condition of Alzheimer’s, dementia, Parkinson’s, stroke and traumatic brain injury patients.”
Alzheimer Science (AS): “Dr. Shinzato, thank you for this interview.”
A current overview of studies and scientific papers on the non-invasive brain stimulation procedure Transcranial Pulse Stimulation (TPS) can be viewed here:
Transcranial Pulse Stimulation (TPS) – Studies
References:
1 Piovesan EC, Freitas BZ, Lemanski FCB, Carazzo CA. Alzheimer’s disease: an epidemiologic analysis on the number of hospitalizations and deaths in Brazil. Arq Neuropsiquiatr. 2023 Jun;81(6):577-584. doi: 10.1055/s-0043-1767827. Epub 2023 Jun 28. PMID: 37379869; PMCID: PMC10306998.
2 Lohse-Busch H, Reime U, Falland R. Symptomatische Behandlung des unresponsiven Wachheitssyndroms mit transkraniell fokussierten extrakorporalen Stoßwellen. NeuroRehabilitation. 2014 Jan 1;35(2):235-44. doi: 10.3233/NRE-141115. PMID: 24990026.
About Gilson Tanaka Shinzato, M.D.
Gilson Tanaka Shinzato, M.D., is a specialist in physical medicine and rehabilitation at the University of São Paulo, Brazil. A specialist in pain therapy and electroneuromyography, he is conducting research on Transcranial Pulse Stimulation (TPS) shock wave therapy under the direction of Prof. Linamara Battistella, President of the Institute of Physical Medicine and Rehabilitation of the Hospital das Clínicas of the Faculty of Medicine of the University of São Paulo (IMREA) and in collaboration with Prof. Orestes Forlenza, a leading researcher in the field of Alzheimer’s disease at the Institute of Psychiatry of the University of São Paulo.
The current TPS study on Alzheimer’s dementia will be followed by further studies on Parkinson’s, stroke and traumatic brain injury as well as on Long COVID, also in collaboration with Prof. Felipe Fregni, a leading neurologist from the University of São Paulo.
The IMREA – HCFMUSP, Department of Forensic Medicine, Bioethics, Occupational Medicine, Physical Medicine and Rehabilitation, FMUSP, the Laboratory of Neurosciences (LIM-27) and the Institute of Psychiatry of HCFMUSP are involved in the TPS studies.
Contact:
Institute of Rehabilitation Medicine (IMREA)
University of São Paulo Medicine School Hospital (HCFMUSP)
Rua Domingo de Soto 100, ZIP code 04116-040, São Paulo, Brazil
Gilson Tanaka Shinzato, PhD Candidate and Research Leader
E-mail: g.shinzato@hc.fm.usp.br
