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Non-thermal focused ultrasound induced reversible reduction of essential tremor in a rat model
Authors:Shirley Sharabi  Dianne Daniels  David Last  David Guez  Zion Zivli  David Castel  Yoav Levy  Alexander Volovick  Javier Grinfeld  Itay Rachmilevich  Talia Amar  Yael Mardor  Sagi Harnof
Institution:1. Advanced Technology Center, Sheba Medical Center, Ramat-Gan, 52621, Israel;2. Neurosurgery Dept, Sheba Medical Center, Ramat-Gan, 52621, Israel;3. Neufeld Cardiac Research Institute, Sheba Medical Center, Ramat-Gan, 52621, Israel;4. InSightec Ltd., Haifa, Israel;5. Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, 69978, Israel;6. Neurosurgery Dept, Rabin Medical Center, Petach-Tikva, 4941492, Israel
Abstract:

Background

Essential tremor (ET) is one of the most common movement disorders of adults, characterized by postural and kinetic tremor. With drug treatment only partially efficient, new treatments are being developed.

Objectives

The goal of this study was to demonstrate the feasibility of non-thermal focused-ultrasound (FUS) to induce tremor-suppression in an ET rat model.

Methods

Harmaline-induced tremor rats were treated with FUS along the inferior olivary (IO) system. EMG was recorded continuously during treatment in order to quantify FUS-induced tremor suppression. T2-weighted MRI was performed immediately following treatment and periodically thereafter.

Results

FUS treatment at an intensity of 27.2?W/cm2 (Isppa) induced significant reduction of tremor in 12 out of 13?ET rats. Tremor frequency was reduced from 6.2?±?2.8 to 2?±?1?Hz, p?<?0.0003. In 6 of the 12 responding rats, tremor was completely suppressed. Response duration was 70?±?61s, on average.FUS induced motor response, depicted as movement of the tail and/or the limbs synchronized with the FUS sonication, was also demonstrated both in ET rats and in naïve rats when treated in the medulla oblongata region.

Conclusions

These results demonstrate the feasibly for obtaining significant tremor reduction or tremor suppression induced by non-thermal, non-invasive, reversible focused-ultrasound.
Keywords:Focused ultrasound  Neuromodulation  Essential tremor  Harmaline  FUS  Focused ultrasound  ET  Essential tremor  Isppa  Intensity spatial peak pulse average  ION  Inferior olivary nuclei
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