Several newborn screening (NBS) programs for Spinal Muscular Atrophy (SMA) have demonstrated feasibility-reliability and short-term efficacy of PCR-based universal SMA NBS, but longer-term data are needed to precise the benefit of this intervention. In addition, the comparison with external control groups can reinforce the level of evidence and support robust health economic assessment. The aim of this study is to compare the medical, quality of life and economic data for SMA patients diagnosed by NBS and those identified by symptoms, in the same country, during the same time period. We collected data on all SMA patients born in Flanders and the Wallonia-Brussels Federation (FWB) between January 1, 2019 (the date on which the entire FWB began screening for SMA) and 30 November 2022 (the date on which Flanders began screening). We compared the median age of diagnosis and initiation of treatment, the treatment, scores on motor development scales, and the age of acquisition of sitting and walking. We also collected quality of life data for parents, utility data for children, and costs associated with the disease. A total of 30 patients were included in the analysis: 16 patients in FWB (7 with 2 SMN2 copies, 4 with 3 copies and 5 with 4 copies) and 13 in Flanders. One patient with a point mutation was not identified by NBS in FWB. Patients in FWB were initially treated by nusinersen (n = 5) risdiplam (n = 3) and onasemnogene abeparvovec (n = 7) at 36 days of life on average (29, 37, and 44 days respectively for patients with 2, 3 and 4 SMN2 copies of SMN2). Two patients shifted from nusinersen to risdiplam, one from nusinersen to onasemnogene abeparvovec and one from risdiplam to onasemnogene abeparvovec. One patient with 4 SMN2 copies was still untreated at 26 months. Median follow up was 32 months (9-54 months). All patients over 18 months with 3 and 4 SMN2 copies acquired ambulation (median age: 17 months, 13-24 months). Of the 7 patients with 2 SMN2 copies, 2 are not yet 18 months old, 4 are walking, and one aged 24 months is not yet walking. One child with 2 SMN2 copies have non-invasive nocturnal ventilation. None of the children needed nutritional support at the time of the last follow-up. Data in Flanders, where NBS was not implemented in the studied time, are currently collected, and will be presented during the congress. Our data shows that middle term outcome of patients identified by NBS is very good so far. Estimation of health care cost saving will be presented.

This study investigated if structural variation in specific gray matter areas is associated with corticosteroid treatment or genotype, and if cerebral morphological variations are related to neuropsychological and behavioral outcomes. The CAT12 toolbox in SPM was used for MRI segmentations, assessing subcortical structures, cortical thickness, gyrification, and sulci depths for DMD patients (n = 40; 9-18 years) and age-matched controls (n = 40). Comparisons were made between DMD vs. controls, daily vs. intermittent corticosteroid treatment (n = 20 each), and Dp140+ vs. Dp140- gene mutations (n = 15 vs. 25). MANCOVA, CAT12 3D statistics and Pearson correlations were conducted. DMD patients showed differences in volumes of distinct subcortical structures, left hemisphere cortical thickness, and gyrification in multiple brain areas compared with healthy controls. The daily treated DMD group exhibited differences in subcortical volumes and different patterns of cortical thickness, sulci depth, and gyrification compared to the intermittent treated DMD group. DMD Dp140+ patients displayed altered gyrification and sulci depth compared to DMD Dp140- patients. Finally, we found correlations between neurobehavioral outcomes and brain areas that showed differences in cortical morphology associated with corticosteroid treatment. Both genotype and corticosteroid treatment are associated with variations in subcortical volumes and cortical morphology, albeit in different ways. Corticosteroid treatment appears to have a more profound association with differences in gray matter characteristics of brain regions that are associated with functional outcomes.

Duchenne muscular dystrophy (DMD) is a severe, progressive neuromuscular disease characterised by loss of ambulation at young age and decline in respiratory and cardiac function. The primary objective of this study is to quantify the per-patient societal cost of DMD in Belgium. The secondary objective is to determine the health-related quality of life (HRQoL) impact on patients and caregivers in Belgium. Patient enrolment commenced at UZ Leuven in November 2023 and is on-going. Participating physicians complete an electronic case record form (eCRF), including demographic, clinical, and healthcare resource utilisation (HRU) data over the last 12 months. A Patient Public Involvement and Engagement survey is completed by the patient (PPIE-P) and caregiver (PPIE-C), capturing cross-sectional patient-reported outcome measures (including HRQoL via the EQ5D-5L and DMDQoL), non-medical, and indirect costs. Patients are stratified by the Project HERCULES natural history of disease model by disease stage (DS). This abstract reports on interim data. eCRF, PPIE-P, and PPIE-C were completed for 25, 21, and 16 patients respectively. Patients were stratified across DS 1 (n=7), DS 2 (n=1), DS 4 (n=7), DS 5 (n=2), DS 6 (n=1), DS 7 (n=5), DS 8 (n=2). Mean (SD) age of the sample was 21.3 years (10.3) and the mean age of diagnosis was 3.7 (3.7). In the last 12 months, the mean number of consultations with all HCPs was 12.0 (12.3), with 16 patients (64%) having ≥1 hospitalisation, 3 patients (12%) having surgery, and 19 patients currently receiving corticosteroids (76%). For patients who completed the EQ5D-5L (n=16), the mean index score was 0.27 (0.21), and for patients who completed the DMDQoL (n=17), the mean index score was 0.61 (0.18). The interim results suggest high HRU associated with DMD patients in Belgium (consultations and hospitalisations), and high impact on EQ5D-5L. The final analysis will include data supplementing the current DS split.

Background: Patients with Duchenne muscular dystrophy (DMD) face a higher risk of neurobehavioral problems, yet an international consensus on screening, assessing, and managing these difficulties is lacking. Objective: This report introduces the term Duchenne Muscular Dystrophy-Associated Neurobehavioral Difficulties (DuMAND) to comprehensively cover the spectrum of neurobehavioral issues in DMD patients, including behavior, psychiatric disorders, and various cognitive, academic, and psychosocial deficits. To facilitate screening, the DuMAND Checklist, a 43-item tool with five subscales, was developed. Methods and results: DuMAND categories were derived through literature review, parent (48 mothers and 37 fathers), and expert (n = 28) input and feedback. The DuMAND Checklist subscales were developed iteratively, incorporating item selection, expert panel (n = 10) assessment for face validity, comprehensiveness, and a pilot validation study in a DMD sample (n = 20). DuMAND encompasses five categories: cognition and learning, social responsiveness, emotion regulation, externalizing behavior, and eating and sleeping. Preliminary validation of the DuMAND Checklist indicates acceptable-to-excellent internal consistency and construct validity. Conclusion: By introducing the DuMAND concept, this study seeks to inspire a consensus approach for screening, assessing, and managing neurobehavioral issues in DMD. Incorporating screening, using the DuMAND Checklist, in addition to medical follow-up will facilitate early intervention, addressing a critical gap in identification of neurobehavioral disorders in DMD. Future research is needed to further evaluate psychometric properties of the DuMAND Checklist and investigate the natural course of DuMAND.