To assess the evolution of bulbar function in nusinersen-treated spinal muscular atrophy type 1 (SMA1).Method: This single-centre retrospective study identified 24 patients (14 females and 10 males) with SMA1, treated with nusinersen between 2017 and 2020. We adapted and validated the Paediatric Functional Oral Intake Scale (p-FOIS), which is an outcome measure to assess bulbar function. Analysis considered SMA1 subtype, nutritional support, and Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and p-FOIS scores at initiation of nusinersen treatment (baseline) and at 6, 12, and 24 months after initiation. Results:The median age at baseline was 11 months (range 1 month-7 years 6 months).Median age at initiation of tube feeding was 8 months (range 0-2 years 2 months).Fourteen patients were tube fed at baseline. The median p-FOIS score was 3 at baseline and 2 at 12 and 24 months. Four patients, all with type 1c SMA, remained orally fed at 24 months. Median CHOP INTEND scores increased from 32 at baseline to 42 at 12 and 24 months.Interpretation: Impaired bulbar function persisted as a significant complication in most nusinersen-treated patients with SMA1, in contrast to the improvement in motor abilities demonstrated in the majority. p-FOIS allows for tracking of bulbar function progression and treatment response. Larger, prospective studies investigating the longer-term impacts of nusinersen on bulbar function are warranted. | 909 BULBAR FUNCTION IN NUSINERSEN-TREATED SMA1 Statistical analysisGroupwise medians and ranges were calculated from the data. The individual trajectories for p-FOIS, motor function, and feeding characteristics were plotted.

Objectives The objective of this study is to analyse retrospective, observational, longitudinal growth (weight, height and BMI) data in ambulatory boys aged 5–12 years with Duchenne muscular dystrophy (DMD). Background We considered glucocorticoids (GC) use, dystrophin isoforms and amenability to exon 8, 44, 45, 51 and 53 skipping drug subgroups, and the impact of growth on loss of ambulation. We analysed 598 boys, with 2604 observations. This analysis considered patients from the UK NorthStar database (2003–2020) on one of five regimes: “GC naïve”, “deflazacort daily” (DD), “deflazacort intermittent” (DI), “prednisolone daily” (PD) and “prednisolone intermittent” (PI). A random slope model was used to model the weight, height and BMI SD scores (using the UK90). Results The daily regime subgroups had significant yearly height stunting compared to the GC naïve subgroup. Notably, the average height change for the DD subgroup was 0.25 SD (95% CI − 0.30, − 0.21) less than reference values. Those with affected expression of Dp427, Dp140 and Dp71 isoforms were 0.77 (95% CI 0.3, 1.24) and 0.82 (95% CI 1.28, 0.36) SD shorter than those with Dp427 and/or Dp140 expression affected respectively. Increased weight was not associated with earlier loss of ambulation, but taller boys still ambulant between the age of 10 and 11 years were more at risk of losing ambulation. Conclusion These findings may provide further guidance to clinicians when counselling and discussing GCs commencement with patients and their carers and may represent a benchmark set of data to evaluate the effects of new generations of GC.

Objective: Characterise the diagnostic and prognostic value of muscle MRI patterns as biomarkers in a genetically heterogeneous nemaline myopathy (NM) patient cohort. Methods: Modified Mercuri scoring of lower limb MRI in genetically characterised NM patients referred to the highly specialised service for congenital myopathies at Great Ormond Street Hospital. Findings were compared to clinical data and MRI patterns derived from collated published data. Results: Twenty-seven patients with MRI were identified (8 NEB-NM, 13 ACTA1-NM, 6 TPM3-NM). NEB-NM demonstrated sparing of the thigh. ACTA1-NM demonstrated diffuse thigh involvement, notable in the vasti, sartorius and biceps-femoris, with relative adductor and gracilis sparing. TPM3-NM demonstrated diffuse thigh involvement notable in biceps-femoris and adductor magnus with relative rectus femoris, adductor longus and gracilis sparing. In the lower leg, the soleus and tibialis anterior are notably involved in all three genotypes. NEB-NM and ACTA1-NM demonstrated relative gastrocnemii and tibialis posterior sparing, while TPM3-NM showed significantly more tibialis posterior involvement (P =< 0.05). Comparison of involvement patterns with literature datasets highlighted preferential adductor and gracilis sparing in our ACTA1-NM cohort, consistent tibialis posterior involvement in our TPM3-NM cohort and a distinct MRI pattern from those derived from other NM genotypes and congenital myopathies. Greater tibialis anterior involvement correlated with foot drop (P = 0.02). Greater tibialis anterior and extensor hallucis longus involvement correlated with worse mobility (P =< 0.04). Interpretation: This is the widest NM MRI data set described to date; we describe distinct muscle involvement patterns for NEB-NM, ACTA1-NM and TPM3-NM which may have utility as diagnostic and prognostic biomarkers and aid in genetic variant interpretation.

The Revised Hammersmith Scale (RHS) is a 36-item ordinal scale developed using clinical expertise and sound psychometrics to investigate motor function in participants with Spinal Muscular Atrophy (SMA). In this study, we investigate median change in the RHS score up to two years in paediatric SMA 2 and 3 participants and contextualise it to the Hammersmith Functional Motor Scale-Expanded (HFMSE). These change scores were considered by SMA type, motor function and baseline RHS score. We consider a new transitional group, spanning crawlers, standers and walkers-with-assistance, and analyse that alongside non-sitters, sitters and walkers. The transitional group exhibit the most definitive change score trend, with an average 1-year decline of 3 points. The RHS has a reduced floor effect compared to the HFMSE, although we show that the RHS should be used in conjunction with the RULM for participants scoring less than 20 points on the RHS. In the stronger participants (between 10 and 42 on the RHS) in the 5-7 age group, both the RHS and HFMSE can detect 1-year change. The timed items in the RHS have high between-participant variability, so participants with the same RHS total can be differentiated by their timed test items.