Inhibitory rTMS in Dystonic Wilson Patients (WILSTIM)

Study of Writing Improvement in Patients With Wilson Disease and Dystonia After One Session of Inhibitory Repetitive Transcranial Magnetic Stimulation

Wilson disease is a genetic disorder resulting in copper accumulation in liver, brain and eye. The neurologic complications include dystonic syndrome, which is a prolonged and excessive muscle activation responsible for abnormal postures. Hand dystonia prevents daily life activities such as writing, which is particularly disabling, since writing is the only mean of communication in these patients with significant slurred speech. Treatment is limited and only partially effective. Low frequency (<or=1Hz) repetitive transcranial magnetic stimulation (rTMS) has shown inhibiting properties when applied over the cortex. Since dystonia has been correlated to hyperactivation of the neurons of the somatosensory cortex (SSC), we hypothesize that one single 20-minute session of 1 Hz rTMS applied on left SSC will improve writing of the right dystonic hand, assessed immediately at the end of the session.

This study investigates the handwriting performance of an homogeneous cohort of patients with Wilson disease and right handed dystonia, after one single inhibitory repetitive transcranial magnetic stimulation (rTMS). Fifteen patients with focal right hand dystonia will receive randomly either active or sham rTMS (1 Hz) to the left somatosensory cortex (SSC) in one single 20 minutes session. Handwriting performance will be measured immediately after this unique session (Visual analogic scale of subjective discomfort in writing, DPRE and WCRS scales, pen pressure and pen velocity measured on touchpad), compared to scores obtained 24 hours before the session. Three days later, the patient will receive the other session (sham rTMS or active rTMS) and the same parameters will be evaluated. This is a single-center, randomized, crossover, prospective, clinical and double-blind study (the rTMS session is performed by the neurophysiologist, but the patient and the neurologist who will perform the handwriting evaluation are blind to the session).

Wilson disease, Dystonia, Movement Disorders, Handwriting, Repetitive Transcranial Magnetic Stimulation

Repetitive Transcranial Magnetic stimulation: 1 Hz rTMS, delivered to left somatosensory cortex during rest. Intervention is delivered during 20 minutes in one single session.

Placebo Transcranial Magnetic stimulation delivered to left somatosensory cortex during rest. Intervention is delivered during 20 minutes in one single session.

Inhibitory 1 Hz rTMS, delivered to left somatosensory cortex during rest. Intervention is delivered during 20 minutes in one single session.

Improvement of handwriting performance immediately after one single 20 minutes session of inhibitory (1 Hz) repetitive transcranial magnetic stimulation over the left somatosensory cortex. quantitative test score of writing WCRS Active or sham stimulation will be randomly assigned to the patient and the other session will be performed 3 days later.

improvement of other quantitative test scores of writing (VAS subjective discomfort writing, DPRE scales and parameters measured on touchpad) after a single session of 1 Hz rTMS inhibitory to the left CSS , compared to the scores achieved in the 24 hours before the session of rTMS. Active or sham stimulation will be randomly assigned to the patient and the other session will be performed 3 days later.

Assessing the improvement of dystonia on the scale WDRS after a single session of 1 Hz rTMS inhibitory to the left CSS, compared to the scores achieved in the 24 hours before the session of rTMS. Active or sham stimulation will be randomly assigned to the patient and the other session will be performed 3 days later.

Assess whether age, disease duration and the presence of cortical atrophy are inversely correlated with the evolution of scores.

Inclusion Criteria: Wilson disease with focal right hand dystonia No modification of medical treatment for 6 months No botulinum toxin administration within the past four months Right handed Focal right hand dystonia Cerebral Magnetic Resonance performed the last 6 months with no other lesion than met in Wilson disease Over 18 Insurance policy holder Informed consent Exclusion Criteria: Pregnant woman Guardianship procedure Seizure history Other cerebral lesions on cerebral MRI than met in Wilson Disease Unable to stay quiet for 30 minutes Handwriting impossible Contra-indications to repetitive Transcranial Magnetic Stimulation