{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T02:48:19Z","timestamp":1792118899627,"version":"4.4.0"},"reference-count":21,"publisher":"American Medical Association (AMA)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2025,12,1]]},"abstract":"<jats:sec>\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Essential tremor (ET) is the most common form of arm tremor. Transcutaneous peripheral nerve stimulation (TPNS) can modulate the central tremor-generating network.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate whether an artificial intelligence (AI)\u2013driven TPNS device is superior to a sham device in reducing ET.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>A randomized clinical trial was conducted from February 7 through August 9, 2024, in 12 outpatient neurology clinics in the United States and China. Participants were adults with upper-extremity tremor and a clinical diagnosis of ET, a tremor severity score of 2 or higher on 1 of the Essential Tremor Rating Assessment Scale (TETRAS) performance subscale tasks, a total performance subscale score of at least 7, and familiarity with operating a smartphone and connecting to Wi-Fi at home. They were randomized 2:1 to receive active TPNS or sham stimulation, stratified by use of ET medications and tremor severity. After the devices were fitted, the participants were instructed to use them during waking hours for 90 days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Intervention<\/jats:title>\n                    <jats:p>A wearable neuromodulation device that stimulates the radial, median, and ulnar nerves and uses AI to continuously adjust stimulation settings in real time.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Outcome and Measures<\/jats:title>\n                    <jats:p>The primary outcome was change in daily activities as measured by the modified Activities of Daily Living (mADL) subscale of TETRAS at 90 days in the intention-to-treat population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 133 screened, 125 were randomized to receive TPNS (n\u2009=\u200983) or sham (n\u2009=\u200942) treatment. The mean (SD) age was 64.9 (13.1) years, 62 (49.6%) were female and 63 (50.4%) male, and the mean (SD) tremor duration was 11.4 (13.1) years. At 90 days, the mADL score was reduced by 6.9 points (95% CI, 5.4-8.4) in the TPNS group vs 2.7 points (95% CI, 1.3-4.0) in the sham group (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001). Skin irritation, the most common device-related adverse event, occurred in 28 of 83 participants (33.7%) in the TPNS group and 2 of 42 (4.8%) in the sham group. Nausea, arthralgia, worsening of existing arthritis in the thumb, muscular weakness, and involuntary muscle contractions each occurred in 1 participant, all in the TPNS group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>The TPNS device improved activities related to upper limb tremor at 90 days and could be an effective noninvasive ET treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov Identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT06235190\">NCT06235190<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamaneurol.2025.3905","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T15:31:07Z","timestamp":1760974267000},"page":"1235","source":"Crossref","is-referenced-by-count":9,"title":["Transcutaneous Peripheral Nerve Stimulation for Essential Tremor"],"prefix":"10.1001","volume":"82","author":[{"given":"William G.","family":"Ondo","sequence":"first","affiliation":[{"name":"Houston Methodist Hospital, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Lv","sequence":"additional","affiliation":[{"name":"Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Tianjin Medical University General Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongsheng","family":"Hu","sequence":"additional","affiliation":[{"name":"Xuanwu Hospital Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart H.","family":"Isaacson","sequence":"additional","affiliation":[{"name":"Parkinson\u2019s Disease and Movement Disorder Center of Boca Raton, Boca Raton, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Yuan","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto J.","family":"Espay","sequence":"additional","affiliation":[{"name":"University of Cincinnati, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Kreitzman","sequence":"additional","affiliation":[{"name":"Parkinson\u2019s Research Centers of America \u2013 Long Island, Long Island, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Han","family":"Kuo","sequence":"additional","affiliation":[{"name":"Columbia University, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salima","family":"Brillman","sequence":"additional","affiliation":[{"name":"Parkinson\u2019s Research Centers of America \u2013 Palo Alto, Palo Alto, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly A.","family":"Shill","sequence":"additional","affiliation":[{"name":"Barrow Neurological Institute, Phoenix, Arizonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly E.","family":"Lyons","sequence":"additional","affiliation":[{"name":"University of Kansas Medical Center, Kansas City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Yang","sequence":"additional","affiliation":[{"name":"Fasikl Inc, Bloomington, Minnesota"},{"name":"University of Minnesota, Minneapolis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Fasikl Inc, Bloomington, Minnesota"},{"name":"University of Minnesota, Minneapolis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Fasikl Inc, Bloomington, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh","family":"Pahwa","sequence":"additional","affiliation":[{"name":"University of Kansas Medical Center, Kansas City"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"key":"noi250071r1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2024.106086","article-title":"Updates in essential tremor.","volume":"122","author":"Okelberry","year":"2024","journal-title":"Parkinsonism Relat Disord"},{"key":"noi250071r2","doi-asserted-by":"publisher","first-page":"28","DOI":"10.5334\/tohm.632","article-title":"How common is essential tremor? 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