Executive Functions in the Chronic Phase of Pediatric Acquired Brain Injury: A randomized controlled trial investigating the efficacy of pediatric Goal Management Training and Associations with Long-term Outcome

Abstract

Pediatric acquired brain injury (pABI), both traumatic and non-traumatic such as brain tumor or stroke, result in more diffuse and enduring impairments compared to adult ABI. These injuries, occurring during ongoing development, typically go beyond the immediate insult, distorting developmental process and resulting in long-term deficits across multiple domains. Executive functions (EFs), which are vital for purposeful, goal-directed, and regulatory behavior in daily life, are often the most severely impacted cognitive aspect following pABI. Despite this, there is a scarcity of proven interventions for executive dysfunction in children, leaving many with unmet rehabilitation needs. There is a pressing need for a deeper understanding of recovery and the long-term implications for the pABI population. Above all, it is crucial to develop evidence-based cognitive rehabilitations methods to address these challenges. The primary objective of this doctoral thesis was to enhance EFs in children and adolescents who were in the chronic phase (> 1 year) of pABI (Paper 1 and II), and expand knowledge by exploring associations between factors pertinent to long-term follow-up and cognitive outcomes (Paper III). Paper I describes the study protocol for the first RCT designed to investigate the efficacy of a metacognitive treatment program (pediatric Goal Management Training, pGMT) in improving EFs in pABI when compared to an active control intervention (psychoeducation pediatric Brain Health Workshop, pBHW). The doctoral work began with a systematically appraisal of previous studies to addresses several methodological shortcomings underscored in reviews and reflected in the trial study design (Paper I and II). Unlike many previous studies, this research broadens its scope to test hypotheses across various pABI etiologies, with high comprehensiveness of data. We conducted a pre-registered, blinded, national multicenter, parallel RCT at pediatric university hospitals. Eligible participants, aged 10 to 17 years with pABI, more than a one year post-onset or ended treatment, and parent-reported EF complaints were randomized into two group-based treatments: the metacognitive intervention, pGMT or the active control, pBHW. Both treatments comprised of 7 sessions over 3 consecutive weeks, followed by 4 weeks of telephone counselling of participants, parents, and teachers and external cuing of participants to enhance implementation. Baseline assessments, immediately post-intervention evaluations, and at 6-months follow-up assessments were conducted. Assessments encompassed the multifaceted nature of EF, with the Behavior Rating Inventory of Executive Function (BRIEF) as the primary outcome measure, and neuropsychological EF tests and a complex naturalistic cooking task as secondary outcomes. The preplanned analyzes were published in a Statistical Analysis Plan. In Paper II, a significant reduction in parent-reported executive dysfunctions in daily life, measured by the BRIEF questionnaire, was demonstrated for both pGMT (n=38) and pBHW (n=38) from baseline to 6 months. Despite the positive outcome, there was no additional effect by the metacognitive training (pGMT) previously shown in adult studies. However, pGMT was associated with enhanced inhibition and executive attention in neuropsychological testing, while pBHW was associated with fewer errors in the naturalistic task. A substantial 96% (n =73) successfully completed the assigned intervention, while 93% (n =71) attended the 6-month follow-up. In paper III, using baseline data from the RCT, we explored associations between age at insult (early, EI; ≤ 7y vs late, LI; >7y), time post-insult, global function (disability; severe, moderate, and good recovery according to Pediatric Glasgow Outcome Scale-Extended), and the outcome measures IQ and EFs (updating, shifting, inhibition and executive attention). The findings indicated that early insult, time exceeding 1-2 years post-insult, and severe disability were associated with poorer IQ and most EFs. With the exception of participants categorized with good recovery, cognitive functions did not appear to resume to age-expected levels with time, regardless of age at insult and time post-insult. Our findings suggest that group-based cognitive rehabilitation, combined with education of parents and teacher involvement is well tolerated and beneficial for enhancing EFs in pABI. However, the study could not conclude on an additional effect of the pediatric adaptation of GMT on BRIEF, as seen in adult studies. Nonetheless, distinct supplementary improvements associated with both interventions require more in-depth investigation in future studies. The comprehensive discussion delves into various aspects contributing to these results, encompassing developmental issues, peculiarities of pGMT, and methodological issues. Our findings emphasize a special attention to children with early pABI and enhancing long-term follow-up. In addition, disability screening may be a helpful tool to identify the need for cognitive rehabilitation. Nevertheless, concluding on pGMT efficacy requires larger studies, considering appropriate assessment levels and possible differences in effect related to treatment duration, developmental factors, etiology and injury characteristics.