Severe Dystonia, Wilson's Disease
Conditions
Keywords
Wilson's Disease, Deep Brain Stimulation, dystonia
Brief summary
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.
Detailed description
4 periods of stimulation on and off, sequence randomized at Day 0.
Interventions
DEVICEMedtronic, Activa® PC on
DEVICEMedtronic, Activa® PC off
Sponsors
Hospices Civils de Lyon
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in movement disorder evaluated by the Canadian Occupational Performance Measure (COPM) performance and satisfaction scores | 21 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in other movement disorder evaluated by the Clinical global impression (CGI) scale | 21 months | — |
| Change in other movement disorder evaluated by the Unified Wilson Disease Rate Scale (UWDRS) | 21 months | The UWDRS consists of 3 sections, including: consciousness, a historical review based on the Barthel scale, and neurological examination. |
| Cognitive evaluation using the Mini Mental Status Examination (MMSE) | Screening visit (2 days) | The MMSE is a brief 30-point questionnaire test commonly used to screen for dementia. |
| Cognitive evaluation using the Frontal Assessment Battery (FAB) | Screening visit (2 days) | The FAB is a brief tool used to assess dysexecutive symptoms. |
| Cognitive evaluation using the BDI-II (Beck Depression Inventory) | Screening visit (2 days) | The BDI-II is a self- report inventory for measuring the severity of depression. |
| Cognitive evaluation using the similarities and matrix reasoning tests from the Wechsler Adult Intelligence Scale (WAIS-IV) | Pre-surgery visit (2 days) | The test of similarities measures concrete, functional, and abstract concept formation. The test of matrix reasoning measures nonverbal analytical reasoning. |
| Cognitive evaluation using the Modified Card Sorting Test (MCST) | Pre-surgery visit (2 days) | The MCST assess problem solving and the ability to shift cognitive strategies in response to changing environmental contingencies. |
| Cognitive evaluation using the Trail Making Test (TMT) | Pre-surgery visit (2 days) | The TMT assess visuo-motor speed and task switching abilities. |
| Cognitive evaluation using the phonemic verbal fluency task | Pre-surgery visit (2 days) | The phonemic verbal fluency task assesses intrinsic response generation. |
| Cognitive evaluation using the 16-items free and cued recall test (RL/RI 16-items) | Pre-surgery visit (2 days) | The RL/RI 16-items test assesses episodic memory and especially abilities to retrieve information from memory. |
| Change in cognitive outcome evaluated by the Tasks of the test of Attentional Performance (TAP) | 21 months | The TAP is a normalized computerized battery to assess attentional and executive abilities. |
| Other movement disorder will be assessed by the reduction of the Burke-Fahn-Marsden (BFM) dystonia scale score | 21 months | 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. |
| Change in behavioral and neuropsychiatric outcome evaluated by the Brief Psychiatric Rating Scale with anchor (BPRS-E(A)) | 21 months | The BPRS-E(A) is widely used to measure psychiatric symptoms and unusual behavior. |
| Change in dysarthria and deglutition outcome evaluated by the spontaneous speech and reading | 21 months | — |
| Change in dysarthria and deglutition outcome evaluated by the the Batterie d'Evaluation de la Dysarthrie (BECD) | 21 months | This BECD score provides a global assessment of dysarthria severity. |
| Change in dysarthria and deglutition outcome evaluated by the Voice Handicap Index (VHI) | 21 months | 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 social outcome evaluated by the Zarit Burden Inventory (ZBI) | 21 months | The ZBI is a popular caregiver self-report measure used by many aging agencies. |
| Change in dysarthria and deglutition outcome evaluated by the maximum phonation time | 21 months | — |
| Change in dysarthria and deglutition outcome evaluated by the GRBAS (Grade, Roughness, Breathiness, Asthenia, Strain) scale | 21 months | Auditory-perceptual evaluation method for hoarseness is the GRBAS scale of the Japan Society of Logopedics and Phoniatrics, which rates hoarseness. |
| Change in dysarthria and deglutition outcome evaluated by the Deglutition Handicap Index (DHI) | 21 months | 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). |
| Change in dysarthria and deglutition outcome evaluated by the timed test of swallowing capacity | 21 months | — |
| Tolerance of Deep Brain Stimulation: occurrence of serious adverse events | 23 months | Clinical examination focusing specifically on vital signs. |
| Change in behavioral and neuropsychiatric outcome evaluated by the Inventaire du Syndrome Dysexécutif Comportemental (ISDC) | 21 months | The ISDC assesses behavioral dysexecutive symptoms. |
Countries
France
Outcome results
None listed