DYSCAR: Characterization of Dystonia
Condition: Dystonia; Parkinson Disease
MeSH terms: Parkinson Disease; Dystonia; Dystonic Disorders
Study type: Observational

Summary: 
      Dystonia is a rare disease leading to a severe handicap. It can be of primary or secondary
      origin. It is characterized by sustained muscle contractions, frequently causing twisting and
      repetitive movements or abnormal postures. These disorders are believed to be caused by some
      dysfunction of the basal ganglia (BG) circuitry, but the mechanisms are largely unknown.

      A better understanding of the disorder requires significant improvements of its
      phenomenological description in relation to aetiology. We want to identify specific motor
      signatures of different forms of dystonia. To that aim, we will ask patients to perform
      movements of various complexities, while recording chronometric, kinematics and EMG data. The
      characteristics of the patients' movements will be compared to those of matched control
      subjects. We will examine abnormal co-activation in distal and proximal muscles to evaluate
      the characteristics of the loss of selectivity of the motor command in mobile vs. fixed
      dystonia. Consistency of the motor output patterns will be compared in three groups of
      patients. We will also study possible cognitive and limbic components of the disease,
      examining the influence of cognitive and emotional loads on movement production. Eventually
      we want to refine the criteria used to classify different forms of the disease, thus enabling
      clinicians to better predict the likely outcome of particular therapeutic procedures.
    

Detailed description: 
      A major difficulty hindering progress in our understanding of dystonia is the fact that
      accurate descriptions of the motor signs associated with different forms of the disease are
      presently lacking. Indeed, different forms of the disease yield symptoms that cannot be
      distinguished on the basis of current clinical evaluations. We hypothesize that the multiple
      pathophysiological mechanisms that appear to underlie the motor symptoms of dystonia should
      induce somewhat different behavioural expressions of the disease, and should also respond
      differently to deep brain stimulation. As proximal muscles are involved in postural limb
      stabilisation, we propose to not only study distal, but also proximal and contra-lateral
      diffusion of the motor command. Our hypothesis is that movement and EMG patterns should
      diverge depending on the aetiology of the disease and task conditions. In other words, we
      expect to identify kinematics and EMG signatures specific to different forms of dystonia.

      One first step towards improving our knowledge of dystonia is thus to scrutinize the motor
      output at the behavioural level, relating abnormal movement patterns to specific aetiologies
      of the disease. Thus, three groups of patients presenting a dystonia of known aetiology (ON
      and OFF dystonia of Parkinson Disease, Primary dystonia, Secondary dystonia) will be included
      in the study, as well as two groups of age-matched control subjects.

      The first step of our experimental approach will consist in studying the kinematics and EMG
      patterns of movements performed by the different groups of patients. For studying motor
      control of the upper limb, we will ask the patients to perform both wrist movements in
      isolation, or in association with a superimposed motor, cognitive or emotional task. The
      organisation and abnormalities of movements of the lower limb will be studied following the
      same rationale, whenever possible. Because of the occurrence of involuntary movements in many
      patients with dystonia, all behavioural recordings will be performed using telemetric
      equipment. This will guarantee that patients will not pull off the captors, nor run any risk
      of getting hurt during the recording sessions.

      The measures will include reaction and movement times, as well as the angular displacements
      of the relevant joints and the bilateral EMG activity of the distal and proximal muscles of
      the limbs. The spatio-temporal characteristics of the patients' movements will be analyzed
      using the recorded chronometric, kinematics and EMG data, and compared to those of
      age-matched control subjects. Muscle activity and movement will be recorded at the different
      levels of the moving and contralateral limbs to thoroughly monitor of the overflow
      characteristics of dystonia.

      Dystonic bradykinesia is thought to be related to a loss of the selectivity of the motor
      command, and in particular its diffusion to antagonist groups. If this hypothesis is correct,
      we expect to observe abnormal co-activation of antagonist groups at the distal level. Because
      of the postural component of dystonia, we also expect to see an undue diffusion of the motor
      command to proximal muscles. Finally, we will look for signs of mirror movements indicating
      perturbations of inter-hemispheric motor inhibition.

      The abnormal co-activation of antagonists and proximal muscles should increase under double
      motor task conditions, where the patient will be asked to perform symmetrical or different
      movements simultaneously with the two limbs. Based on the hypothesis that symmetrical
      coupling of motor effectors is easier to control than asymmetrical patterns, which require
      inter-hemispheric inhibition of the irrelevant movement, motor performance should be more
      difficult and diffusion of the motor command should be increased in the asymmetrical motor
      tasks.

      Under each condition of movement, the consistency of the recorded patterns of kinematics and
      EMG data will be compared between the three groups of patients. Regarding secondary dystonia,
      whenever relevant, we will also correlate the observed patterns with existing cerebral
      lesions. We will attempt to find further connections between the clinical phenotype of the
      patients and the measured movement parameters. For example, the kinematics and EMG data will
      be put into relation to the main types of symptoms displayed by the patients (mobile vs.
      fixed dystonia), and the distribution of the symptoms.

      The hypothesis that dystonia is a pure motor disease will be tested using double task
      experimental protocols. Patients will be requested to perform the same arm movement, while 1)
      performing a simultaneous cognitive task, such as counting backwards or detecting a specific
      visual stimulus, diverting some of the attentional resources.
    

Intervention name(s): EMG and Kinematics recording
Intervention type(s): Other
Intervention description(s): The experimental protocol envisages the recording of the movement and the bilateral recording of activity EMG during three types of tasks:
discrete driving tasks: movements of inflection and extension of the wrist car-generated, or produced in answer to an imperative stimulus try driving repetitive: sequence of inflection-extension of the wrist unilateral, bilateral in phase and bilateral in opposition of phase.
try driving complexes: movement of inflection and extension of the wrist with concurrent realization of a driving task controlatérale different, or of a cognitive task.
For the Parkinsonian patients, these various tests will be carried out twice: without antiparkinsonian treatment ("off") and under treatment ("one").
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Parkinsonian patients, Dystonia patients,Major depression, Dementia, Acute psychosis,
        Clinical motor deficit making the movements impossible, joint or muscle pathology