From Movement Preparation to Gait Execution in ALS
Condition: Amyotrophic Lateral Sclerosis
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis
Study type: Observational

Summary: 
      This research program will focus on gait initiation and postural control in Amyotrophic
      Lateral Sclerosis (ALS) patients, by comparing patients with vs without postural instability
      (but also in comparison to controls), by using a multidisciplinary approach which combines
      neurophysiological and neuroimaging analyses.

      After clinical evaluation, two groups of ALS patients, defined upon the feature of postural
      instability, and one group of healthy subjects (n=25 for each group of patients and 20 for
      healthy subjects) will be included in the study.

      The neurophysiological evaluation will be performed through a gait initiation assessment,
      which will alow us to collect biomechanical and electromyographical data, such as the braking
      index.

      The neuroradiological evaluation will include first an fMRI analysis, a study of specific
      circuits in networks will be performed which will provide the first description of neural
      network dynamics associated with the preparation and execution of movement in ALS patients.

      The investigators major research hypothesis is:

        -  By comparing patients with vs without postural instability, but also in comparison to
           controls, the investigators main research neurophysiological hypothesis is that patients
           with postural instability will display an impaired braking.

        -  This impaired braking could be partly explained by a dysfunction and/or lesion of the
           basal ganglia and brain stem structures, corresponding to the investigators main
           neuroradiological hypothesis.
    

Detailed description: 
      Compared to other movement disorders, such as Parkinson Disease (PD), the mechanisms of
      movement impairment in Amyotrophic Lateral Sclerosis (ALS) have not been a focus of great
      interest. It is at least partly related to the classical assumption that impairment of
      movement in ALS simply reflects a dysfunction of the final motor pathways. However, the
      concept that ALS purely involves upper and lower motor neuron has been definitively
      challenged. Accumulating evidence for the concept that ALS is a multisystem degenerative
      disease is supported by histological, neurophysiological and neuroimaging studies.
      Clinically, lower limb stiffness is associated with extrapyramidal rigidity and postural
      instability in 69% of ALS patients. These latter may also display abnormalities of movement
      initiation impairing walking, such as gait initiation failure, usually reported in PD
      patients. All these data support the hypothesis that some balance troubles in ALS patients
      may result from an additional dysfunction and/or lesion of the basal ganglia circuitry and/or
      of its output structures, such as the cortex or the midbrain.

      In PD patients, which represent a model of basal ganglia system dysfunction, length and
      velocity of the first step during gait initiation are known to be reduced and improved by
      dopaminergic therapy whereas postural instability is less sensitive to the treatment
      suggesting the involvement of other brain structures dysfunction and/or lesion. One way to
      evaluate the postural control during the gait initiation process is to measure the vertical
      velocity of the centre of gravity by using a force platform. In healthy adults, during the
      single support phase, a forward fall of the centre of gravity occurs and is actively reversed
      by the stance leg soleus muscle activation prior foot contact. In parkinsonian patients with
      postural instability, this phenomenon, called active braking, is altered. It is assumed that
      this postural instability results from additional lesions and/or dysfunction in the basal
      ganglia output structures, especially in the midbrain, containing the pedunculopontine
      nucleus and the mesencephalic locomotor region, two structures known to participate to the
      control of locomotion and posture in animals.

      This research program will focus on gait initiation and postural control in ALS patients, by
      comparing patients with vs without postural instability (but also in comparison to controls),
      by using a multidisciplinary approach which combines neurophysiological and neuroimaging
      analyses.

      After clinical evaluation, two groups of ALS patients, defined upon the feature of postural
      instability, and one group of healthy subjects (n=25 for each group of patients and 20 for
      healthy subjects) will be included in the study.

      The neurophysiological evaluation will be performed through a gait initiation assessment,
      which will alow us to collect biomechanical and electromyographical data, such as the braking
      index.

      The neuroradiological evaluation will include first an fMRI analysis. A study of specific
      circuits in networks will be performed which will provide the first description of neural
      network dynamics associated with the preparation and execution of movement in ALS patients.

      If the investigators get a deeper understanding of the neural substrates underlying the
      hypothetical impairment of gait initiation and postural control, the investigators will then
      be able to develop adequate therapeutical strategies (pharmacological interventions, surgical
      therapies, rehabilitation programs) aimed at improving movement preparation and gait
      execution in ALS patients
    

Observational model: Other
Time perspective: Other
Sampling method: Non-Probability Sample
Study population: 
        ALS patients with motor deficit with or without postural instability
      
Keywords: movement preparation; gait; gait initiation; postural control; neuroimaging