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.
4 periods of stimulation on and off, sequence randomized at Day 0.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
5
Hospices Civils de Lyon
Lyon, France
Hopital Lariboisiere
Paris, France
Hôpital Fondation Adolphe de Rothschild Paris
Paris, France
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.
Time frame: 21 months
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.
Time frame: 21 months
Change in other movement disorder evaluated by the Clinical global impression (CGI) scale
Time frame: 21 months
Change in other movement disorder evaluated by the Unified Wilson Disease Rate Scale (UWDRS)
The UWDRS consists of 3 sections, including: consciousness, a historical review based on the Barthel scale, and neurological examination.
Time frame: 21 months
Cognitive evaluation using the Mini Mental Status Examination (MMSE)
The MMSE is a brief 30-point questionnaire test commonly used to screen for dementia.
Time frame: Screening visit (2 days)
Cognitive evaluation using the Frontal Assessment Battery (FAB)
The FAB is a brief tool used to assess dysexecutive symptoms.
Time frame: Screening visit (2 days)
Cognitive evaluation using the BDI-II (Beck Depression Inventory)
The BDI-II is a self- report inventory for measuring the severity of depression.
Time frame: Screening visit (2 days)
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.
Time frame: Pre-surgery visit (2 days)
Cognitive evaluation using the Modified Card Sorting Test (MCST)
The MCST assess problem solving and the ability to shift cognitive strategies in response to changing environmental contingencies.
Time frame: Pre-surgery visit (2 days)
Cognitive evaluation using the Trail Making Test (TMT)
The TMT assess visuo-motor speed and task switching abilities.
Time frame: Pre-surgery visit (2 days)
Cognitive evaluation using the phonemic verbal fluency task
The phonemic verbal fluency task assesses intrinsic response generation.
Time frame: Pre-surgery visit (2 days)
Cognitive evaluation using the 16-items free and cued recall test (RL/RI 16-items)
The RL/RI 16-items test assesses episodic memory and especially abilities to retrieve information from memory.
Time frame: Pre-surgery visit (2 days)
Change in cognitive outcome evaluated by the Tasks of the test of Attentional Performance (TAP)
The TAP is a normalized computerized battery to assess attentional and executive abilities.
Time frame: 21 months
Change in behavioral and neuropsychiatric outcome evaluated by the "Inventaire du Syndrome Dysexécutif Comportemental" (ISDC)
The ISDC assesses behavioral dysexecutive symptoms.
Time frame: 21 months
Change in behavioral and neuropsychiatric outcome evaluated by the Brief Psychiatric Rating Scale with anchor (BPRS-E(A))
The BPRS-E(A) is widely used to measure psychiatric symptoms and unusual behavior.
Time frame: 21 months
Change in dysarthria and deglutition outcome evaluated by the spontaneous speech and reading
Time frame: 21 months
Change in dysarthria and deglutition outcome evaluated by the the "Batterie d'Evaluation de la Dysarthrie" (BECD)
This BECD score provides a global assessment of dysarthria severity.
Time frame: 21 months
Change in dysarthria and deglutition outcome evaluated by the Voice Handicap Index (VHI)
The VHI is a questionnaire to quantify the functional, physical and emotional impacts of a voice disorder on a patient's quality of life.
Time frame: 21 months
Change in dysarthria and deglutition outcome evaluated by the maximum phonation time
Time frame: 21 months
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.
Time frame: 21 months
Change in dysarthria and deglutition outcome evaluated by the Deglutition Handicap Index (DHI)
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).
Time frame: 21 months
Change in dysarthria and deglutition outcome evaluated by the timed test of swallowing capacity
Time frame: 21 months
Change in social outcome evaluated by the Zarit Burden Inventory (ZBI)
The ZBI is a popular caregiver self-report measure used by many aging agencies.
Time frame: 21 months
Tolerance of Deep Brain Stimulation: occurrence of serious adverse events
Clinical examination focusing specifically on vital signs.
Time frame: 23 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.