Administration of 4 mA tDCS to a person with progressive supranuclear palsy leads to improved walking speed

Progressive supranuclear palsy (PSP) is an untreatable neurodegenerative disease that produces cognitive decline along with parkinsonian-like motor impairments in areas such as gait and articulation. We examined whether transcranial direct current stimulation (tDCS), by influencing the firing of cortical neurons, could improve gait (defined here as walking speed) in a person living with PSP. Three previous studies have examined tDCS in individuals with PSP and found positive results [1Valero-Cabré A. Sanches C. Godard J. et al.Language boosting by transcranial stimulation in progressive supranuclear palsy.Neurology. 2019; 93: e537-e547Crossref PubMed Scopus (8) Google Scholar, 2Madden D.L. Sale M.V. O'Sullivan J. Robinson G.A. Improved language production with transcranial direct current stimulation in progressive supranuclear palsy.Neuropsychologia. 2019; 127: 148-157Crossref PubMed Scopus (8) Google Scholar, 3Alexoudi A. Patrikelis P. Deftereos S. et al.Effects of anodal transcranial direct current stimulation on cognitive dysfunction in patients with progressive supranuclear palsy.Psychiatrike = Psychiatriki. 2019; 30: 320-328Crossref PubMed Scopus (3) Google Scholar]. However, in two of these studies, the primary outcome was language ability rather than motor function. More relevant, Alexoudi et al. (2019) administered tDCS over the motor cortices and reported improvements for dysarthria and dysphagia. Notably, however, all three studies lacked a control condition that verified the results were due to the administration of tDCS, nor examined how results changed post-stimulation. In this case report, we examined over time the walking speed of a person with PSP when they walked 24 m in a hallway. The participant was a post-menopausal 61-year old female with a two year history of mild to moderate PSP. She was physically active and walked daily, but she did so with a walker. Our primary outcome measure was gait interval time: while walking 24 m, we recorded the time needed to walk every 3 m and divided the sum of these times by 8 to produce the average interval time (i.e., the average time needed to walk 3 m). A supplementary video shows this task. This task took place during 20-min tDCS sessions, where the participant first walked 24 m in a hallway, followed by a computer button-pressing task (FLANKER) to sustain motor activity that engaged her fingers. As we report below, tDCS did appear to improve walking speed. The following is the supplementary data related to this article:https://www.brainstimjrnl.com/cms/asset/3cd0d700-4c33-48e1-b5fe-638f7a6b3fb2/mmc1.mp4Loading ...(mp4, 16.04 MB) Download video https://www.brainstimjrnl.com/cms/asset/3cd0d700-4c33-48e1-b5fe-638f7a6b3fb2/mmc1.mp4Loading ...(mp4, 16.04 MB) Download video tDCS sessions initially took place four times a week (Monday-Thursday) for three weeks. In the first week, SHAM stimulation was administered and walk times were recorded on the fourth session (I.e., Thursday) to obtain a baseline measure that also incorporated any possible practice effects from completing the tasks. Sessions again took place during weeks 2 and 3, but with real tDCS, and times were recorded on Thursday of week 3. To obtain post-stimulation scores, the participant returned and repeated the same session every month afterwards, which allowed us to examine change over time as the stimulation effect washed-out. Originally, we planned to resume stimulation after the participant had returned to baseline levels; however, after observing a slow-down that was followed by a stabilization for three months, we chose to begin a second round of tDCS sessions. Thus, a second course of 8 tDCS stimulation sessions was administered over two weeks, with interval time again measured on the final session of weeks 1 and 2. In this manner, we could examine change in walking speed over time in an ABA format: when administering tDCS after establishing a baseline, during a non-stimulation wash-out period, and finally when tDCS was re-administered. Stimulation intensity was 4 mA, delivered via a Soterix tDCS machine, with anode electrodes (5 × 7cm) placed over the left and right deltoid muscles, and a cathode electrode (5 × 7cm) placed just ahead of the motor cortex at FCz. Electrodes were placed within saline-soaked sponges (0.9%). We chose this montage because neurotargeting modeling software (HD-Explore, Soterix) suggested placing an anode electrode on each deltoid muscle with a corresponding cathode electrode over the motor cortex would lead the current to travel up the spinal cord, contact the hindbrain areas, before exiting via the cathode electrode. Stimulating well these hindbrain areas was critical because they are known to be most affected brain areas in PSP. This montage may also reduce shunting that would have occurred had the current first passed through the skull. Meanwhile, an intensity level of 4 mA was chosen to maximize the resulting electric field intensity (i.e., how well tDCS would stimulate the targeted brain areas). To date, only a handful of tDCS studies have used this intensity level, but report it be safe, well tolerated, and without serious adverse effects [4Nitsche M.A. Bikson M. Extending the parameters range for tDCS: safety and tolerability of 4 mA stimulation.Brain Stimulation. 2017; 10: 541-542Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar, 5Khadka N. Borges H. Paneri B. et al.Adaptive current tDCS up to 4 mA.Brain Stimulation. 2020; 13: 69-79Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar, 6Workman C.D. Kamholz J. Rudroff T. The tolerability and efficacy of 4 mA transcranial direct current stimulation on leg muscle fatigability.Brain Sci. 2019; 10: 12https://doi.org/10.3390/brainsci10010012Crossref Scopus (17) Google Scholar, 7Workman C.D. Fietsam A.C. Rudroff T. Transcranial direct current stimulation at 4 mA induces greater leg muscle fatigability in women compared to men.Brain Sci. 2020; 10: 244https://doi.org/10.3390/brainsci10040244Crossref Scopus (11) Google Scholar], with some studies reporting stronger results when 4 mA rather than 2 mA was administered [[8]Workman C.D. Fietsam A.C. Uc E.Y. Rudroff T. Cerebellar transcranial direct current stimulation in people with Parkinson's disease: a pilot study.Brain Sci. 2020; 10: 96https://doi.org/10.3390/brainsci10020096Crossref Scopus (20) Google Scholar]. Note, however, that the 4mA stimulation received was split to the two separate anode electrodes on the deltoid muscles; thus, each electrode only received 2 mA tDCS. Nevertheless, stimulation likely coalesced as it approached the single cathode electrode. The participant tolerated well the stimulation received. The average interval times are displayed in Fig. 1 below: As can be observed in Fig. 1, large improvements occurred when tDCS was administered for two weeks following the initial SHAM week. Compared with baseline, there was 40% reduction, which represents faster walking, and the benefit persisted for two months, with faster interval times at each post-stimulation evaluation. Also, rather than returning to pre-therapy baseline levels, performance plateaued at a 15% faster interval time four months post-stimulation, which remained stable for three months. At that point, we chose to resume doing the sessions with tDCS for two weeks, which lead to the first repeated observation of a faster interval time (5%) in the participant. By administering tDCS in an ABA format (stimulation, wash-out, resumed stimulation), we were able to observe results when stimulation was first administered, how they changed over time post-stimulation, and how they changed again when stimulation was resumed. Improvement continued two-months post-stimulation, followed by a slow-down and stabilization, and times only became faster again when tDCS was resumed. Thus, our preliminary data indicates that 8 sessions of tDCS might improve motor function in people with PSP in terms of faster walking speed, represented here by faster interval times. This result is important because there is currently no effective symptomatic therapy available for PSP. Considering the potential dangers of falls, a frequent occurrence for this population, improved motor abilities would be quite beneficial. Ultimately, this result promotes further investigating tDCS as a feasible novel therapy for people with PSP. Howard Chertkow is Senior Scientist and Chair in Cognitive Neurology and Innovation, Rotman Research Institute, Baycrest Health Sciences; Dr. Chertkow is supported by a Foundation Grant from the CIHR (Canadian Institutes for Health Research), along with the Weston Foundation and the Baycrest Health Sciences Foundation. The data was collected at the Lady Davis Institute and Jewish General Hospital Memory Clinic at McGill University in Montreal, and at the Rotman Research Institute at Baycrest Health Sciences in Toronto Dr. Chertkow has participated as a site PI in pharmaceutical trial activities in the past five years sponsored by: Hoffmann-La Roche Limited, TauRx, and Immunocal (site investigator for trials). For all other authors, declaration of interest is none. We thank Shelley Solomon for recording the video showing KoL in her tDCS session. We also thank Julia Singerman for her assistance in the tDCS training sessions.

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