WILSTIM - DBS (WILson STIMulation - Deep Brain Stimulation) (WILSTIM DBS)

DEEP BRAIN STIMULATION FOR SEVERE DYSTONIA ASSOCIATED WITH WILSON'S DISEASE. A Prospective Multicenter Meta-analysis of Nof1 Trials

Dystonia in Wilson's disease represent a major issue. The persistence of disabling motor symptoms despite medical treatments justifies conducting a study on deep brain stimulation (DBS) in Wilson's disease (WD). For bradykinetic patients, subthalamic nucleus (STN) could be considered as a better target than the globus pallidus (GPi). For patients with hyperkinetic dystonia, the internal globus pallidus (GPi) will be chosen as the target of DBS. The investigators hypothesize that STN DBS will improve Wilson's disease patients, who, despite copper chelators drugs, are still impaired by severe dystonia and akinesia (more or less associated with other movement disorders). The investigators primary objective is to demonstrate the efficacy of STN/GPi DBS on dystonia associated with Wilson's disease. Secondary objectives: To evaluate the impact of STN/GPi DBS on other movements disorders (tremor, Parkinsonism, chorea) observed in Wilson's disease. To describe cognitive status of patients and to evaluate the consequences of STN/GPi DBS on cognition and behavioral aspects of the disease. To evaluate the consequences of the stimulation on speech and swallowing. To evaluate the social impact of STN/GPi DBS in Wilson's disease. To evaluate the safety of STN/GPi DBS in the specific context of Wilson's disease.

Change in movement disorder evaluated by the Canadian Occupational Performance Measure (COPM) performance and satisfaction scores

Efficacy will be assessed by the change in the COPM performance and satisfaction scores after each 4 month-period of stimulation on and off, using blinded evaluations. The COPM is a standardized outcome measure widely used in occupational therapy. This tool can facilitate the identification of functional difficulties and individualized subject-specific priorities for intervention, which may not be captured with other standardized scales.

Other movement disorder will be assessed by the reduction of the Burke-Fahn-Marsden (BFM) dystonia scale score

The reduction of the Burke-Fahn-Marsden (BFM) dystonia scale score is evaluated after each 4 month-period of stimulation on and off, using blinded video evaluations. This scale is the standard of assessments on dystonia and Parkinson.

The UWDRS consists of 3 sections, including: consciousness, a historical review based on the Barthel scale, and neurological examination.

Cognitive evaluation using the similarities and matrix reasoning tests from the Wechsler Adult Intelligence Scale (WAIS-IV)

The test of similarities measures concrete, functional, and abstract concept formation. The test of matrix reasoning measures nonverbal analytical reasoning.

The MCST assess problem solving and the ability to shift cognitive strategies in response to changing environmental contingencies.

The RL/RI 16-items test assesses episodic memory and especially abilities to retrieve information from memory.

Change in behavioral and neuropsychiatric outcome evaluated by the "Inventaire du Syndrome Dysexécutif Comportemental" (ISDC)

Change in behavioral and neuropsychiatric outcome evaluated by the Brief Psychiatric Rating Scale with anchor (BPRS-E(A))

Change in dysarthria and deglutition outcome evaluated by the the "Batterie d'Evaluation de la Dysarthrie" (BECD)

The VHI is a questionnaire to quantify the functional, physical and emotional impacts of a voice disorder on a patient's quality of life.

Change in dysarthria and deglutition outcome evaluated by the GRBAS (Grade, Roughness, Breathiness, Asthenia, Strain) scale

Auditory-perceptual evaluation method for hoarseness is the GRBAS scale of the Japan Society of Logopedics and Phoniatrics, which rates hoarseness.

The DHI questionnaire is composed of statements on deglutition related aspects in daily life. It is subdivided in three domains: physical (S) (symptoms related to swallowing), functional (F) (nutritional and respiratory consequences) and emotional (E) (psychosocial consequences).

Inclusion Criteria: Age > 18 and < 60 years. Severe neurological form of Wilson's disease with predominant dystonia and akinetic-rigid syndrome, despite optimized treatment stabilized for at least 6 months. Important disability due to abnormal movements (Rankin score=2 to 4). Absence of dementia (MMS > 24 and BREF > 15). Stable psychiatric status and absence of severe depression (BDI <28). Social security coverage. Signature of informed consent. (signature of legal guardian for subjects under protection) Exclusion Criteria: Severe hepatopathy with coagulation disorders (Platelet count < 100 G / l; INR > 1.5; V factor deficit; low level of fibrinogen < 1g/dL; increased of fibrin degradation products; low level of antithrombin). Liver transplanted patients < 2 years Patients under immunosupressive drugs and corticoids regimen. Participation to another biomedical research involving any drugs. Severe and uncontrolled psychosis or depression. Major atrophy on brain MRI that could represent a problem for leads implantation. Necrosis of the STN/GPi on brain MRI. Female subjects who are pregnant or lactating.