TY - JOUR
T1 - Brain metabolic changes with longitudinal transcutaneous afferent patterned stimulation in essential tremor subjects
AU - Barath, Abhijeet S.
AU - Rusheen, Aaron E.
AU - Min, Hoon Ki
AU - Lee, Jeyeon
AU - Ross, Erika
AU - Shin, Sooyoon
AU - Loudermilk, Adam
AU - Wessel, Bambi
AU - Lowe, Val J.
AU - Lee, Kendal H.
AU - Blaha, Charles D.
N1 - Funding Information:
This study was supported by Cala Health, Inc., 875 Mahler Rd Suite 168, Burlingame, CA, 94010, USA. Dr. Ross is a former employee of Cala Health and currently is employed by Abbott. Dr. Shin is employed by Cala Health, Inc. Dr. Lowe serves as a consultant for Bayer Schering Pharma, Philips Molecular Imaging, Piramal Imaging and GE Healthcare and receives research support from GE Healthcare, Siemens Molecular Imaging, and AVID Radiopharmaceuticals. Dr. Kendall H. Lee is a principal shareholder in Navinetics.
Funding Information:
This study was funded by Cala Health, Inc. and two of the authors (SS and ER) are current/past employees of Cala Health. The objectivity of the study, reporting, and analysis of the data are protected from the above described competing interest through an agreement between Mayo Clinic and Cala Health. All other authors have no competing interests.
Funding Information:
We would like to acknowledge Cala Health Inc., Burlingame, CA for providing technical, financial, and material support for this study. We would also like to acknowledge the use of REDCap software supported by Federal Grant UL1TR002377 to Mayo Clinic Center for Clinical and Translational Science (CCATS) for management of subject information pertinent to this project. Training for A.S.B. was supported by The Boston Scientific Fellowship Grant. Training grant funding for A.E.R was supported by NIH F31NS115202-01A1, NIH R25GM055252-23, NIH TL1TR002380-03, and NIH T32GM065841-17.
Funding Information:
We would like to acknowledge Cala Health Inc., Burlingame, CA for providing technical, financial, and material support for this study. We would also like to acknowledge the use of REDCap software supported by Federal Grant UL1TR002377 to Mayo Clinic Center for Clinical and Translational Science (CCATS) for management of subject information pertinent to this project. Training for A.S.B. was supported by The Boston Scientific Fellowship Grant. Training grant funding for A.E.R was supported by NIH F31NS115202-01A1, NIH R25GM055252-23, NIH TL1TR002380-03, and NIH T32GM065841-17. Financial Disclosures This study was supported by Cala Health, Inc., 875 Mahler Rd Suite 168, Burlingame, CA, 94010, USA. Dr. Ross is a former employee of Cala Health and currently is employed by Abbott. Dr. Shin is employed by Cala Health, Inc. Dr. Lowe serves as a consultant for Bayer Schering Pharma, Philips Molecular Imaging, Piramal Imaging and GE Healthcare and receives research support from GE Healthcare, Siemens Molecular Imaging, and AVID Radiopharmaceuticals. Dr. Kendall H. Lee is a principal shareholder in Navinetics. Competing Interests This study was funded by Cala Health, Inc. and two of the authors (SS and ER) are current/past employees of Cala Health. The objectivity of the study, reporting, and analysis of the data are protected from the above described competing interest through an agreement between Mayo Clinic and Cala Health. All other authors have no competing interests.
Publisher Copyright:
© 2020 The Author(s).
PY - 2020/12/16
Y1 - 2020/12/16
N2 - Background: Non-invasive peripheral nerve stimulation, also referred to as transcutaneous afferent patterned stimulation (TAPS), reduces hand tremor in essential tremor (ET) subjects. However, the mechanism of action of TAPS is unknown. Here, we investigated changes in brain metabolism over three months of TAPS use in ET subjects. Methods: This was an interventional, open label, single group study enrolling 5 ET subjects. They received 40 minutes of TAPS treatment twice daily for 90 days. Brain metabolic activity and tremor severity were measured using 18F-fluorodeoxyglucose (FDG) PET/CT, and the Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS), respectively, at baseline and after 90 days. Tremor power and frequency was measured before and after all TAPS sessions using an onboard three-axis accelerometer. Results: FDG PET/CT revealed areas of hypermetabolism in ipsilateral cerebellar hemisphere and hypometabolism in contralateral cerebellar hemisphere following 90 days of TAPS treatment, compared to day one (uncorrected p value <0.05). Paired pre-post kinematic measurements over 90 days showed significantly decreased tremor power (p < 0.0001) but no change in tremor frequency. The TETRAS score on day 1 decreased from 6.5 ± 2.5 to 4.1 ± 1.8 following TAPS (p = 0.05). The pre-post TETRAS scores on day 90: 4.9 ± 1.5 and 4.1± 1 were lower than pre-TAPS TETRAS score on day 1 (p = 0.14 and 0.05, respectively). Conclusions: Our results suggest that longitudinal TAPS of the median and radial nerves modulates brain metabolism in areas instrumental to motor coordination and implicated in ET. Clinically, TAPS reduced tremor power, but had no effect on tremor frequency. This study paves the way for comprehensive studies in larger cohorts to further elucidate the mechanism of TAPS. Highlights: Non-invasive peripheral nerve stimulation, also referred to as transcutaneous afferent patterned stimulation (TAPS), reduces hand tremor in essential tremor subjects. Longitudinal TAPS therapy alters cerebellar metabolism, which can be a cause or consequence of tremor reduction. Cerebellar-premotor region connectivity may play a role in the anti-tremor effects of TAPS.
AB - Background: Non-invasive peripheral nerve stimulation, also referred to as transcutaneous afferent patterned stimulation (TAPS), reduces hand tremor in essential tremor (ET) subjects. However, the mechanism of action of TAPS is unknown. Here, we investigated changes in brain metabolism over three months of TAPS use in ET subjects. Methods: This was an interventional, open label, single group study enrolling 5 ET subjects. They received 40 minutes of TAPS treatment twice daily for 90 days. Brain metabolic activity and tremor severity were measured using 18F-fluorodeoxyglucose (FDG) PET/CT, and the Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS), respectively, at baseline and after 90 days. Tremor power and frequency was measured before and after all TAPS sessions using an onboard three-axis accelerometer. Results: FDG PET/CT revealed areas of hypermetabolism in ipsilateral cerebellar hemisphere and hypometabolism in contralateral cerebellar hemisphere following 90 days of TAPS treatment, compared to day one (uncorrected p value <0.05). Paired pre-post kinematic measurements over 90 days showed significantly decreased tremor power (p < 0.0001) but no change in tremor frequency. The TETRAS score on day 1 decreased from 6.5 ± 2.5 to 4.1 ± 1.8 following TAPS (p = 0.05). The pre-post TETRAS scores on day 90: 4.9 ± 1.5 and 4.1± 1 were lower than pre-TAPS TETRAS score on day 1 (p = 0.14 and 0.05, respectively). Conclusions: Our results suggest that longitudinal TAPS of the median and radial nerves modulates brain metabolism in areas instrumental to motor coordination and implicated in ET. Clinically, TAPS reduced tremor power, but had no effect on tremor frequency. This study paves the way for comprehensive studies in larger cohorts to further elucidate the mechanism of TAPS. Highlights: Non-invasive peripheral nerve stimulation, also referred to as transcutaneous afferent patterned stimulation (TAPS), reduces hand tremor in essential tremor subjects. Longitudinal TAPS therapy alters cerebellar metabolism, which can be a cause or consequence of tremor reduction. Cerebellar-premotor region connectivity may play a role in the anti-tremor effects of TAPS.
KW - Deep brain stimulation
KW - Essential tremor
KW - Noninvasive stimulation
KW - Positroemission tomography
KW - Transcutaneous afferent patterned stimulation
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U2 - 10.5334/tohm.565
DO - 10.5334/tohm.565
M3 - Article
C2 - 33362946
AN - SCOPUS:85099077056
SN - 2160-8288
VL - 10
SP - 1
EP - 10
JO - Tremor and Other Hyperkinetic Movements
JF - Tremor and Other Hyperkinetic Movements
ER -