rTMS in Wilmson Diasease Dysarthria

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Brief Title

rTMS in Wilmson Diasease Dysarthria

Official Title

Inhibitory rTMS Applied on Laryngeal Motor Cortex in Wilson's Disease Patients With Dysarthria

Brief Summary

      Wilson disease is a hereditary hepatic and neurological disease associated with copper
      accumulation. Neurological symptoms are of extra-pyramidal, cerebellar and dystonic origin.
      Dysarthria is one of the debilitating symptoms of Wilson disease poorly responsive to
      pharmacological treatment. The most common form is a dystonic hyperkinetic Dysarthria.

      Pathophysiology of dystonia is still not elucidated. Motor cortex hyperexcitability has been
      demonstrated in various forms of dystonia. Furthermore, rTMS inhibitory applied over motor
      cortex has been shown to transitory reduce dystonic symptoms in various forms of dystonia.

      In the present study, we investigate the effect of a single 1Hz 20-minutes inhibitory rTMS
      session applied over the motor laryngeal cortex on dyasarthria is the main kinetic dysarthria
      has been shown to be associated with inhibition of laryngeal motor cortex in Parkinson

Detailed Description

      A consecutive series of Wilson disease patients with dystonic hyperkinetic dysarthria will be
      prospectively recruited.

      Patients will receive 3 days apart to two rTMS sessions.

      rTMS procedures will be performed with a figure of eight coiled. A single 20-minutes 1 Hz
      biphasic stimulation (1200 pulses) session will be applied over the laryngeal motor cortex. A
      brain imaging positioning device will be used during all the procedure A second stimulation
      session will be performed 3 days apart.

      Patients will be centrally randomized to receive first either the active stimulation (80% of
      the resting motor threshold) or the sham stimulation (using a visually identical coil to
      reproduce the click sound and the scalp sensation of the active coil).

      A TMS evaluation of cortical silent period over the left motor cortex will be performed
      before the first rTMS session.

      Before and immediately after each stimulation (active or sham) patient will received an
      clinical evaluation including Clinical Assessment Battery for Dysarthria intelligibility
      score, "A" phonation time, diadococinesia , bucco-linguo-facial motricity score and UWDRS.

      A standard 20-minutes EEG will be performed before the first rTMS session and immediately
      after the second rTMS session.

Study Type


Primary Outcome

Improvement of the Clinical Assessment Battery for Dysarthria intelligibility score

Secondary Outcome

 Improvement of the Clinical Assessment Battery for Dysarthria intelligibility sub-scores


Wilson Disease



Study Arms / Comparison Groups

 Experimental stimulation
Description:  Patients receive an inhibitor treatment of rTMS using activ coil (MCF B65 coil) for 30 minutes at 1Hz at 80% of the resting motor threshold (MagPro stimulator; MagVenture A / S, Farum, Denmark) onto the left laryngeal cortex located thanks to a neuronavigation device (Syneika one [SYN1], Syneika, Cesson-Sévigné, France).


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

October 1, 2022

Completion Date

October 1, 2023

Primary Completion Date

November 1, 2022

Eligibility Criteria

        Inclusion Criteria:

          -  Conseting adult patients with social insurance

          -  Wilson disease with dystonic hyperkinetic dysarthria

          -  Stable pharmacological therapy n the last 6 monts

          -  Brain MRI in the previous 6 months, without additional brain lesion

          -  Patients that did not receive botulinium toxin in the previous 4 months

        Exclusion Criteria:

          -  Incapacitated adult

          -  Previous mdedical history of epilepsia

          -  Pregnancy or breastfeeding

          -  Brain lesion outside basal ganglia on brain MRI

          -  Patient consider by the investigator not able to sustain an 30 minutes rTMS session
             without moving

          -  Vocal chord lesion

          -  Previous history of laryngeal surgery

          -  rTMS contra indication




18 Years - N/A

Accepts Healthy Volunteers



, +33(0) 1 49 95 80 76, [email protected]

Location Countries


Location Countries


Administrative Informations



Organization ID


Responsible Party


Study Sponsor

Assistance Publique - Hôpitaux de Paris

Study Sponsor

, , 

Verification Date

September 2022