Randomised Controlled Clinical Trial of Cognitive Rehabilitation in Multiple Sclerosis
Condition: Multiple Sclerosis; Cognitive Rehabilitation
MeSH terms: Multiple Sclerosis; Sclerosis
Study type: Interventional

Summary: 
      Despite the need for cognitive rehabilitation, there is a paucity of well-designed research
      studies to investigate treatment approaches or their effectiveness in MS. Most of published
      studies suffer from significant methodological flaws including small sample size, short
      follow-up periods, and lack of specific outcome criteria to determine improvement. O'Brien et
      al. (2008) recently reviewed 16 studies of cognitive rehabilitation designed to persons with
      MS and found only 4 class I studies and only one class I study of rehabilitation of attention
      deficits. Methodologically rigorous research is needed to confirm the preliminary results
      reported by these studies and determine the effectiveness and efficacy of cognitive
      rehabilitation interventions in attention deficits in MS. O'Brien et al. listed limitations
      found in previous studies that must be addressed in future studies. The present study was
      designed according to these recommendations. It is a randomized, controlled study, in
      parallel groups, evaluator blinded.

      Number of participants: 25 RRMS patients in the active group, 25 RRMS patients in the control
      group and 25 healthy subjects.

      The protocol will be proposed to RRMS patients AFFILIATED TO FRENCH SOCIAL SECURITY referred
      to the investigators center by practicing neurologists and fulfilling the inclusion criteria
      for screening.

      Patients will be randomised between two groups. The active group (25 patients) will be
      treated by rehabilitation. Individual rehabilitation procedures will be focused on attention,
      executive functions and IPS. The program will be tailored to each patient cognitive status
      depending on the impairments identified during the initial assessment while maintaining a
      systematic work on attention and executive functions. A total of 50 sessions lasting one hour
      at a rate of 3 sessions per week for a total period of 4 months will be proposed. Patients
      randomized in the other group will participate to group session every week without specific
      cognitive rehabilitation. 25 healthy control subjects (group C), matched to patients for
      education, gender and age with patients of groups A/B will have the same evaluation
      procedures than patients.

      Evaluation will be performed at baseline, after 4 months (end of treatment period) and after
      8 months. Evaluation will include clinical testing, cognitive battery (paper/pencil and
      computer tests), cognitive ecological evaluation (Computer test of attention in a virtual
      reality environment and driving test on a driving simulator), questionnaires about daily life
      and MRI (fMRI and MRI). All patients and healthy subjects will undergo the fMRI protocol
      using a paradigm previously published by the investigators group (Bonnet et al., 2009):
      Go/No-go paradigm with increasing difficulty during four successive conditions (the Tonic
      Alertness task, Go/No-go (IG), reversal Go/No-go (RG), and complex Go/No-go (CG). In a
      previous study the investigators observed compensatory activation in MS patients as compared
      to healthy controls for the three first conditions and a saturation of compensatory processes
      for the more complex. In the present study, the investigators hypothesize that a similar
      pattern will occur at baseline and that cognitive rehabilitation will improve brain
      compensation at the fourth level of complexity.
    

Detailed description: 
      : Multiple Sclerosis (MS) is the most frequent disabling neurological disease in young
      adults. Over the past two decades, cognitive impairment in MS has received increasing
      interest. Although for a long time described in MS text books, it has been underestimated
      until recently. It is now accepted as an important feature of MS with a high impact on
      working and social abilities. The cognitive disorders in MS are dominated by a slowdown in
      information processing speed (IPS), as well as disturbances of attention and memory. The
      nature of cognitive findings suggest that the impairments depend on the integrity of
      large-scale cortical integrative processes, which involve long-distance white matter
      projections which can be impaired due to diffuse demyelinating injury in patients with MS. At
      the early stages of MS there is increasing evidence that neuroplasticity, the ability of the
      brain to respond to various insults, allows adaptive reorganization of cognitive functions to
      limit impairment, despite widespread tissue damage. Recently, we showed that at the early
      stages of RRMS compensatory capacities are relatively maintained, especially in
      highly-educated patients suggesting that cognitive training might be useful. The requirement
      of cerebral compensatory mechanisms to perform the cognitive tests was postulated in MS
      patients on the basis of functional MRI (fMRI) studies. By using a go/no go task of
      increasing complexity in a fMRI study in RRMS patients, we observed that a limitation of this
      compensatory cerebral recruitment appears when the attentional solicitations reach a
      particular level of difficulty. We postulate that a cognitive training program may help to
      maintain these compensatory capacities. Therefore, we propose to evaluate the effect of the
      program on brain activation using a task with several levels of attention requirement
      (increased attention load) by using fMRI and to evaluate in parallel its clinical effect and
      its impact in daily activities.
    

Intervention name(s): specific cognitive rehabilitation; non specific cognitive rehabilitation; no intervention
Intervention type(s): Behavioral; Behavioral; Other
Intervention description(s): Individual rehabilitation procedures will be focused on attention, executive functions, IPS and working memory. The program will be tailored to each patient cognitive status depending on the impairments identified during the initial assessment while maintaining a systematic work on attention and executive functions. A total of 50 sessions lasting one hour at a rate of 3 sessions per week for a total period of 4 months will be proposed. Sessions will include varied exercises according to complexity and presentation modality, using computerized and "paper-and-pencil" tasks and metacognitive training. Work will be progressive, depending on the progresses achieved (increase complexity and intensity of the exercises according to success at the previous level of exercises).; A total of 50 sessions lasting one hour at a rate of 3 sessions per week for a total period of 4 months will be proposed by group composed to 5 patients; no intervention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Multiple sclerosis; functional MRI; cognitive rehabilitation; ecological evaluation; neuroplasticity