Transcranial magnetic stimulation as a feasible, non-invasive, neuromodulatory intervention in fetal alcohol spectrum disorders. A very first proof of concept.

INTRODUCTION: A neurobiological feature of Fetal Alcohol Spectrum Disorder (FASD) is a global decrease in neuronal connectivity, which leads to significant impairments in everyday functionality. Non-invasive repetitive transcranial magnetic stimulation (rTMS) could potentially positively influence neuronal plasticity but has not yet been studied in FASD. The present trial addresses this gap, making it the first-ever study of rTMS in FASD. MATERIALS AND METHODS: The prospective clinical trial was conducted at the LMU University Hospital Munich and enrolled eight FASD participants aged 6-16. Six sessions of 1 Hz-rTMS over the left dorsolateral prefrontal cortex were administered two times a week for three weeks consisting of 1500 pulses at 90 % of resting motor threshold in four trains of 375s. Outcome measures investigated feasibility and treatment response of rTMS on executive functions, attention/impulsivity, social-emotional regulation and quality of life (QoL) via standardized tests and the FASD parents' app. RESULTS: Adherence and retention rate were 100 %. Adverse events (AEs) were mild and self-limiting, resulting in a per-session risk of 53.3 %, with local paraesthesia accounting for 54.2 % of the AEs. There were individual relevant but no significant group-level improvements in the investigated functional cerebral domains or participants' QoL. The FASD parents' app showed no significant change in participants' daily functioning or caregivers' QoL. Caregivers' parental stress decreased significantly. CONCLUSION: FASD is a very complex disorder that is difficult to treat. In addition, comorbidities as atypical responses to pharmacotherapies are frequent. For this reason, non-invasive, innovative therapies for children with FASD have to be developed. For the first time, rTMS was shown to be safe, tolerable, and acceptable and thus well feasible in paediatric patients with FASD. Further clinical studies with larger samples are needed to identify effective stimulation protocols and to evaluate treatment response.

Prognostic factors for long-term outcome in children with fetal alcohol spectrum disorders.

INTRODUCTION: Known protective factors for long-term outcome in children with fetal alcohol spectrum disorders (FASD) are early diagnosis and a stable, non-violent supportive environment. Which factors contribute to the stability of care is not yet known. Thus, the aim of our study was to evaluate whether the age at diagnosis and the complexity of brain dysfunction play a role for placement changes in children with FASD. MATERIALS AND METHODS: An online survey was conducted among caregivers and professionals caring for children with FASD and seeking help at the German FASD Competence Centre Bavaria (N = 232). The survey collected information about diagnosis, brain dysfunctions, behavioural factors influencing everyday life and changes of placement. The association of timing of diagnosis, brain dysfunctions and neurobehavioral impairment with changes of placement (<2 vs. 2 or more changes) was evaluated via logistic regression models. RESULTS: About 50% of the children received their diagnosis of FASD after the age of 5 years. The complexity of brain dysfunctions in children with FASD affecting everyday life was high. 15% of the children experienced four or more changes of placement. Children with more neuropsychological impairments experienced more changes of placement (OR: 2.53, 95% CI: 1.36-4.71). CONCLUSIONS: Even though our results need to be interpreted with caution due to methodological limitations such as the use of a convenience sample and limited statistical power, they imply that severely affected children with FASD experience a less stable environment. These children may therefore be at high risk for a negative prognosis. To warrant a better prognosis for the affected children, professionals urgently need to pay attention to early recognition and the complexity of neuropsychological impairments in children with FASD as well as to the support that caregivers urgently need.