Telerehabilitation of Working Memory in Children With Periventricular Leukomalacia and Bilateral Cerebral Palsy
Condition: Periventricular Leukomalacia
MeSH terms: Cerebral Palsy; Leukomalacia, Periventricular
Study type: Interventional

Summary: 
      Periventricular Leukomalacia (PVL) is a white matter lesion surrounding the lateral
      ventricles of the brain occurring in the prenatal period, associated with a disorder of
      movement and posture, known as bilateral cerebral palsy. Children with PVL and bilateral
      cerebral palsy have spared verbal abilities, as measured by verbal Intelligence Quotient
      (verbal IQ) tests, while non-verbal intelligence and especially visuo-perceptual and
      visuo-spatial abilities are impaired. In addition some studies underline the impact of PVL
      also on executive function, especially in terms of working memory and in the ability to
      inhibit distraction.

      Working Memory is the ability to retain and manipulate information for brief periods of time.
      It is important in several complex cognitive functions, such as academic learning and in
      planning and organizing daily life activities. School-based activities, indeed, such as math
      and reading depend on a student's ability to pay attention to several instructions or
      information and to hold and integrate them in their mind.

      Recent behavioural and neurofunctional studies describes the effect of an evidence-based and
      computer-based training on working memory, the Cogmed Working MemoryTraining. Functional MRI
      show increase in parietal and prefrontal activity after this training, while the behavioural
      data demonstrate the generalization of this effect also on cognitive functions not directly
      trained, as attention, inhibition, learning and non-verbal reasoning. Cogmed Working
      MemoryTraining (RoboMemo®, CogMed-Cognitive Medical Systems, Stockholm, Sweden) is an online
      treatment comprising a number of visuo-spatial and verbal exercises that vary automatically
      depending on the individual child's performance in any given task. The training period is
      intensive and includes 25 home session for five weeks, 30-45 minutes each day. A
      Cogmed-trained coach monitors training progress and participants' commitment daily.

      Only one ongoing study has used the CogMed training in children with cerebral palsy, but
      without investigating the correlation between behavioural findings with neurofunctional data.

      The aim of this study is to analyze the effect of the working memory training with CogMed on
      trained and not directly trained cognitive abilities and on the changes in cortical
      electrophysiological reorganization during the sleep after training. The sleep analysis will
      be focused in particular on the slow waves activity [frequency range of 1-4.5 Hz] and on the
      sleep spindle [frequency range of 12-14Hz], which reflect the depth of sleep and are related
      to memory processes, learning and brain plasticity.

      The results of this project will shed light on the mechanisms of neuroplasticity, by
      enhancing knowledge on the neuropsychological effects of a specific working memory training
      and on the neurophysiological underpinnings of these behavioural effects in a clinical
      population of children with congenital brain lesions, as PVL.
    

Detailed description: 
      The procedures implemented to register patients data will include the following steps:

        -  The quality assurance plan will provide: - to verify that all clinical fields, necessary
           to include and select patients, are available in the registry (e.g. type of cerebral
           palsy; MRI documentation, age); - to monitor that patients' contact information are
           available as well as testing materials and software; - to set team meetings to uniform
           recruitment procedure, data collection and registration.

        -  Data checks will be conducted by two or more researches from the team;

        -  Source data verification: both paper and electronic case report forms will be used and
           mutually checked.

        -  Data dictionary: Pre-post measures will be chosen by the team and described in a report
           form together with references and normative data.

        -  Procedure Standardization to address registry operations: Researches will co-work in
           patient recruitment and will attribute an identification number to each patient enrolled
           according to the inclusion and exclusion criteria evaluated by the neuropsychiatric team
           and described below. All researchers will be trained to register data in an internal
           database and to note the presence of adverse events. The researcher providing the
           training will assure comprehension and subscription of the written consent. Consent form
           will be discussed by the team in order to provide explicit and clear instructions on the
           training protocol to parents and patients.

        -  Calculation of sample size: Sample size, to specify the number of participants necessary
           to demonstrate the training effect, will be calculated from the training effect size
           between the Start index and the Max index provided by CogMed training. Based on a
           previous pilot study in our institute (effect size =.54) and on findings by Lundqvist
           and collaborators (2010) (effect size=.95), the effect size estimates for this study
           will be .60 and the sample size 20 children.

        -  Design: A stepped randomized clinical trial design will be chose to split the
           participants in two groups, matching for age and sex, in order to control test-retest
           effects. Both groups will receive neuropsychological and electrophysiological
           assessments at the same initial time point (T1). One group (Cluster B) will be start
           Cogmed training at home immediately after T1, while the second group (Cluster A) will
           start the training in the following time point (T2). When the training will be
           completed, both groups will be retested with neuropsychological and electrophysiological
           assessments (T2). After this time point, the Cluster A will start Cogmed training and
           will be re-tested with the same neuropsychological and the electrophysiological
           assessments at the finally time points (T3).

        -  The following time points will be provided:

      Initial time point (T1) will correspond to pre-training assessment for both Clusters; Second
      time point (T2) will be provided after 6 or 7 weeks from T1 and will coincide with
      post-training assessment for the Cluster B and an other pre-training assessment for the
      Cluster A; Finally time point (T3), after 6 or 7 weeks from T2, will constitute the
      post-training assessment for Cluster A.

        -  Intervention program: Cogmed Working MemoryTraining (RoboMemo®, CogMed-Cognitive Medical
           Systems, Stockholm, Sweden) is an online treatment comprising a number of visuo-spatial
           and verbal exercises that vary automatically depending on the individual child's
           performance in any given task. The training period is intensive and includes 25 home
           session for five weeks, 30-45 minutes each day. A Cogmed-trained coach monitors training
           progress and participants' commitment daily for all the training period, corresponding
           to time period T1-T2 for Cluster B and T2-T3 for Cluster A.

        -  Plan for Missing data: Unavailable or not interpretable (significantly out of range)
           pre-post training data (behavioural or neurophysiological) will be considered as
           missing. The patients who will not complete the training will be excluded from the
           analysis.

        -  Plan for Statistical analysis: Univariate and Multivariate statistical analysis will be
           performed to compare neuropsychological performance and electrophysiological patterns at
           the different time points . Correlational analysis will be also performed to study the
           association between neuropsychological and electrophysiological data.
    

Intervention name(s): Cluster B CogMed: an home-based and computer-based solution to improve working memory deficit; Cluster A No training. Delay start of CogMed
Intervention type(s): Other; Other
Intervention description(s): CogMed: an home-based and computer-based solution to improve working memory deficit; No training will be provided after T1 time point. Cluster A will start the CogMed training after the assessment at the T2 time point
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: working memory training; home-based training; periventricular leukomalacia; bilateral cerebral palsy; neuropsychological profile; high density EEG; slow waves activities