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.