ABSTRACT Objective Onasemnogene abeparvovec (OA) is an AAV9‐based gene therapy for spinal muscular atrophy type I (SMA I). Real‐world outcomes show increased response variability compared to clinical trials, and follow‐up data beyond 12–18 months are limited. The aim of this 24‐month prospective observational study is to comprehensively describe the clinical outcomes of an Italian cohort of SMA I patients treated with OA. Methods Based on recent literature, patients' treatment status was categorized as: monotherapy (OA only), bridge therapy (transition to OA within 3 months of starting nusinersen or risdiplam), or switch therapy (transition to OA after > 3 months of 1st treatment). Linear mixed‐effects models examined predictors of improvement (CHOP‐INTEND), adjusting for baseline motor function, SMN2 copy number, age, and prior treatment. Descriptive analyses were used to show changes in motor, respiratory, and nutritional milestones. Results The cohort included 64 patients: 27 monotherapy, 9 bridge, and 28 switch. All patients showed significant improvement over 24 months (β = 20.40 points/year, p < 0.001). Patients who switched showed slower improvement (β = −3.76, p = 0.038) compared to monotherapy, while those who bridged showed no difference. Older age at treatment was associated with slower improvement (β = −1.48 points/year per month, p = 0.002). Of 49 non‐sitters at baseline, 39 (80%) achieved sitting and 5 (10%) achieved walking. No new safety signals emerged in the second year of follow‐up. Interpretation Age and baseline motor functional status significantly influence outcomes; however, substantial confounding, particularly the initial treatment, limits the ability to isolate individual effects. Longer follow‐up is essential for evaluating therapeutic responses in heterogeneous SMA I populations.

Background/Objectives: The advent of disease modifying therapies (DMTs) for Spinal Muscular Atrophy (SMA) has highlighted the need for reliable tools to assess bulbar function in type I individuals. The Oral and Swallowing Abilities Tool (OrSAT) was originally developed to evaluate swallowing and feeding abilities in infants with SMA type I during the first two years of life. This study aimed to assess the applicability of the OrSAT in a cohort of children with SMA type I older than 2 years. Methods: Fifty-two children with genetically confirmed SMA type I, aged 2 to 12.6 years, were included. All participants had received at least one DMT, administered either soon after diagnosis or when treatment became available. Bulbar and feeding abilities were assessed using the OrSAT and results were grouped according to clinical subtype and feeding modality. Given the small sample size of the subgroups and the ordinal nature of OrSAT scores, comparisons between groups were performed using the non-parametric Kruskal-Wallis test. Results: At follow-up, 27 children were orally fed, 19 were exclusively tube-fed, and 6 were tube-fed but were also able to eat some food by mouth. The OrSAT scores reflect a wide spectrum of bulbar function from severe to no impairment. Most children who required exclusive tube-feeding at follow-up had already been tube-fed at treatment initiation, while a small number showed improvement in swallowing abilities and the partial recovery of oral feeding during follow-up. Conclusions: Our results suggest that the OrSAT, previously used only in the first two years of life, may also be applicable in older children to describe bulbar involvement and monitor changes over time. However, further studies are needed to refine the tool for this age group and to formally validate its use in older children with SMA type I. Its use may contribute to the longitudinal assessment of swallowing abilities and support rehabilitative management.

AIM:To describe bulbar function trajectories in patients with spinal muscular atrophy (SMA) type 1 treated with nusinersen in the UK and Italy. METHOD:In two previously reported, retrospective, observational cohort studies, we observed the 2-year change in the Children's Eating and Drinking Ability Scale (CEDAS) (the revised and optimized version of the Paediatric Functional Oral Intake Scale [p-FOIS]) and Oral and Swallowing Ability Tool (OrSAT) in 44 patients treated on average at 8.3 months (interquartile range = 4.1-14.4 months), with data collected every 6 months from treatment initiation. [Correction added on 30 June 2025 after first online publication: In the preceding sentence, 11.2 months (interquartile range = 4.1-24.7 months) has been changed to 8.3 months (interquartile range = 4.1-14.4 months).] RESULTS: The Italian cohort had more participants in the 1b group (symptom onset >2 weeks and <3 months), while the UK had more participants in the 1c group (symptom onset <6 months). Over 2 years, the p-FOIS/CEDAS captured lack of bulbar improvement in the 1b group, with 40% displaying stability and 45% showing decline; in the 1c group, stability was captured (71%). OrSAT captured improvement in 47% of the 1b group and 43% of the 1c group at 2 years; this was predominantly because of age-related speech acquisition and feeding viscosities, where the item was not age-appropriate at baseline. INTERPRETATION:The p-FOIS/CEDAS and OrSAT measures capture complementary information on the effect of disease-modifying treatments (DMTs) on bulbar function. Further studies are required to understand bulbar function trajectories in symptomatic and presymptomatic cohorts with SMA receiving different DMTs.

Becker Muscular Dystrophy (BMD) is a genetic disorder, caused by mutations in the dystrophin gene. Cardiac involvement is a common feature in this condition, often manifesting as dilated cardiomyopathy (DCM) or arrhythmias. In patients with BMD, ventricular dysfunction is frequently attributed to non–ischemic mechanisms, given the known pathophysiology of dystrophinopathy. However, overlooking coexisting ischemic heart disease, particularly in older patients with cardiovascular risk factors, can result in suboptimal management. A 57–year–old patient, hypertensive, with high cholesterol and with a family history of idiopathic dilated cardiomyopathy, affected by BMD, presented for a cardiological evaluation as part of follow–up for his dystrophinopathy, asymptomatic for cardiac symptoms. The echocardiogram showed a worsening of left ventricular contractile function compared to the previous year’s check–up left ventricular ejection fraction (LVEF) was 42% vs 55%, with hypokinesia of the mid–basal lateral wall. Considering these findings, cardiac magnetic resonance (MRI) was recommended. The MRI confirmed left ventricular contractile dysfunction: LVEF 36%, with intramural late gadolinium enhancement (LGE) in the basal lateral, inferior, and septal segments, as well as the mid–inferolateral segment. Due to these findings, and despite the highly likely nature of the LV dysfunction related to the known muscular dystrophy, the patient underwent CT angiography to rule out coronary disease. The coronary CT angiography revealed bivasal coronary artery disease. Therefore, coronary angiography was performed and percutaneous coronary intervention (PCI) was performed on proximal and mid–RCA, distal LAD, and proximal D1 that had critical stenoses. DISCUSSION: This case demonstrates that cardiomyopathy secondary to coronary artery disease can coexist with dystrophin–related cardiomyopathy, especially in older patients with traditional cardiovascular risk factors. This case underscores the need to maintain a broad differential diagnosis when evaluating left ventricular dysfunction in BMD patients. The findings highlight the need for a comprehensive cardiovascular assessment. The importance of multimodal imaging: LGE patterns in cardiac MRI, while suggestive of fibrosis, may overlap with ischemic scarring, necessitating further evaluation with coronary imaging.

The advent of newborn screening for spinal muscular atrophy (SMA) has highlighted the need for easy, quick, clinical tools to be used in infants with SMA identified in the neonatal period. We propose a new short module developed using items from the Hammersmith Neonatal Neurological Examination (HNNE) and from a module developed for floppy infants, both previously used in newborns with SMA. The new module was developed by identifying and selecting the items that were more often found to have abnormal findings in SMA newborns. The proforma was designed by selecting 13 items and converting them into a format that would facilitate the interpretation of the results. The cohort included 25 infants. Based on HNNE and add-on module results, 13 were classified as asymptomatic, 5 as pauci-symptomatic, and 7 as symptomatic. All symptomatic infants showed abnormalities in posture, tone, tremors, and reflexes, along with reduced antigravity movements and abnormal breathing. Among pauci-symptomatic infants, all had abnormal reflexes, three also had tremors, and one showed mild hypotonia. There was excellent inter-observer reliability assessed using intra-class correlation coefficients with 95% confidence intervals (0.947) and full concordance with the original full-length forms. CONCLUSION:Our findings support the use of the short form in clinical practice, especially when time or resources are limited. It can be used in multiple occasions, allowing to detect the onset of possible signs in asymptomatic infants and to follow their progression. WHAT IS KNOWN:• Newborns with SMA identified by neonatal screening may show clinical signs at diagnosis. • These signs may be subtle and easily missed on standard neonatal examination. WHAT IS NEW:• The new form includes a short examination that can reliably detect initial signs of SMA. • The new examination can be used to detect the onset and the progression of clinical signs.

Duchenne muscular dystrophy (DMD) is an X–linked recessive neuromuscular disorder associated with early and progressive degeneration of skeletal, smooth, and cardiac muscles, with progressive loss of ambulation, respiratory failure, and dilated cardiomyopathy. To date, there is limited data in the literature regarding the impact of different classes of cardioactive drugs on left ventricular dysfunction associated with DMD. Specifically, the only drugs shown to have a prognostic impact are corticosteroids and ACE inhibitors, whose use is recommended from the age of 10. However, most DMD patients experience a progressive decline in left ventricular function starting in the second decade of life. The scarcity of data in the literature, combined with the complexity of therapeutic management, often prevents the implementation of optimal heart failure therapy. To evaluate whether treatment with SGLT inhibitors (dapagliflozin) is well–tolerated and effective in patients with DMD and asymptomatic left ventricular systolic dysfunction. From 2022 to 2024, we enrolled 23 non–ambulatory patients with DMD (mean age 25±4.28) and a left ventricular ejection fraction ranging from 22% to 40% on echocardiography, without symptoms of heart failure. All patients were already on optimal medical therapy with Sacubitril/Valsartan or ACEi/ARB, beta–blockers, and anti–aldosterone agents at the maximum tolerated dose, according to the 2021 ESC heart failure guidelines. Therapy with dapagliflozin was introduced at the standard dose of 10 mg/day, with baseline renal function assessed using cystatin C. Clinical and echocardiographic follow–up was performed at 6 and 12 months. At baseline assessment, the mean left ventricular ejection fraction (LVEF) was 31%. A significant improvement in LVEF was observed after 6 months (35%; p‹0.005) and at 12 months (38%; p‹0.005). A significant reduction in heart failure biomarker levels (NT–proBNP) was observed at 6 months (mean baseline value 703 pg/mL vs 374 pg/mL at 6 months, p=0.004); however, this reduction was not maintained at 12 months. Renal function, assessed using cystatin C, remained stable during follow–up. In one patient, the drug was discontinued due to poor tolerance. Our data suggest that, in patients with DMD and reduced ejection fraction, therapy with dapagliflozin may improve left ventricular function, with a satisfactory safety profile.

Neonatal screening for SMA has allowed the identification of infants who may present with early clinical signs. Our aim was to establish whether the presence and the severity of early clinical signs have an effect on the development of motor milestones. Infants identified through newborn screening were prospectively assessed using a structured neonatal neurological examination and an additional module developed for the assessment of floppy infants. As part of the follow-up, all infants were assessed using the HINE-2 to establish developmental milestones. Only infants with at least 24 months of follow-up were included. Normal early neurological examination (n = 11) was associated with independent walking before the age of 18 months while infants with early clinical signs of SMA (n = 4) did not achieve ambulation (duration follow-up 33.2 months). Paucisymptomatic patients (n = 3) achieved ambulation, one before the age of 18 months and the other 2 between 22 and 24 months. Conclusion: Our findings suggest that early clinical signs may contribute to predict motor milestones development.

The aim of this study was to assess the need for tube feeding in a cohort of treated infants with type I SMA and to identify predictive factors. All patients were classified at baseline, when treatment started, and at follow-up according to their functional level and the need for tube feeding. Fisher’s exact test was used to examine the associations between the outcome at the last follow-up and SMA type, SMN2 copy number, and baseline nutritional status. ANOVA was performed to compare CHOP INTEND scores and age at treatment initiation with outcomes. The cohort includes 75 type I SMA infants treated between 0.1 and 5 years of age. At the last follow-up, 34 had no need for tube feeding, 9 had tube feeding but were also able to be fed by mouth, and 32 had tube feeding and were unable to be fed by mouth. Thirty of the 41 infants with tube feeding at follow-up already had feeding difficulties when treatment was started. The need for tube feeding at follow-up was associated with the level of feeding involvement at baseline and with CHOP INTEND scores [p < 0.001] but not with SMN2 copy number, SMA type 1 subtypes or age at treatment. The results of this study suggest that the need for tube feeding is not frequent in treated infants with type I SMA and, when occurring, can be predicted by the level of feeding involvement and low CHOP INTEND scores at baseline.

Objective The aim of this study was to assess early language acquisitions in treated individuals with spinal muscular atrophy (SMA) type 1 and in infants identified by newborn screening (NBS). Methods Parents of SMA individuals aged between 8 and 36 months were asked to fill in the MacArthur-Bates Communicative Development Inventory (MB-CDI) that assesses comprehension, gesture and expressive skills. A follow-up assessment was performed in 21 of the 36. Results The MB-CDI was completed by parents of 24 type 1 and 12 infants identified by NBS. Comprehension skills were preserved in 81% of the type 1 SMA and in 87% infants identified by NBS. Gesture abilities were <5th centile in 55% of the type 1 SMA and in none of those identified by NBS. Lexical expressions were <5th centile in more than 80% type 1 SMA and in 50% of infants identified by NBS. At follow-up, despite an increase in lexical expression skills, the scores remained below the fifth centile in 43% type 1 SMA and in 86% of infants identified by NBS. Conclusions These results suggest that language and communication development may follow a similar pattern to that observed in motor function with the possibility to develop skills (eg, ability to say clear words) that are not usually present in untreated infants but with a level of performance that does not reach that of their typically developing peers.

Mitochondrial fission and fusion are vital dynamic processes for mitochondrial quality control and for the maintenance of cellular respiration; they also play an important role in the formation and maintenance of cells with high energy demand including cardiomyocytes and neurons. The DNM1L (dynamin-1 like) gene encodes for the DRP1 protein, an evolutionary conserved member of the dynamin family that is responsible for the fission of mitochondria; it is ubiquitous but highly expressed in the developing neonatal heart. De novo heterozygous pathogenic variants in the DNM1L gene have been previously reported to be associated with neonatal or infantile-onset encephalopathy characterized by hypotonia, developmental delay and refractory epilepsy. However, cardiac involvement has been previously reported only in one case. Next-Generation Sequencing (NGS) was used to genetically assess a baby girl characterized by developmental delay with spastic–dystonic, tetraparesis and hypertrophic cardiomyopathy of the left ventricle. Histochemical analysis and spectrophotometric determination of electron transport chain were performed to characterize the muscle biopsy; moreover, the morphology of mitochondria and peroxisomes was evaluated in cultured fibroblasts as well. Herein, we expand the phenotype of DNM1L-related disorder, describing the case of a girl with a heterozygous mutation in DNM1L and affected by progressive infantile encephalopathy, with cardiomyopathy and fatal paroxysmal vomiting correlated with bulbar transitory abnormal T2 hyperintensities and diffusion-weighted imaging (DWI) restriction areas, but without epilepsy. In patients with DNM1L mutations, careful evaluation for cardiac involvement is recommended.

Progressive bulbar involvement is frequent in spinal muscular atrophy, with prevalence and severity of deficits associated with type. The report provides an overview of the presentations made at the workshop grouped into 4 sessions: the first section was dedicated to videofluoroscopy with a revision of the existing protocols and discussion on which one should be used in routine clinical practice and in research settings. The second session was dedicated to interprofessional routine assessments of bulbar function, with a review of the recent clinical tools specifically developed for SMA. The third section was focused on the assessments performed by speech and language therapists/pathologists in the new SMA phenotypes. The last section focused on how the new therapies have changed the approach in rehabilitation for bulbar dysfunction. Finally, we present the consensus that was achieved on these aspects and possible action points from these.

The increasing pressure to include non ambulant Duchenne muscular dystrophy (DMD) boys in clinical trials has highlighted the need for outcome measures that could address the impact of upper limb function on activities of daily living. The aim of the present study was to establish the correlation between the recently developed Patient Reported Outcome Measure for the upper limb (PROM UL) and the observer rated functional scale Performance of Upper Limb (PUL 2.0) in a large cohort of DMD boys and young adults. As part of a larger natural history study, non ambulant DMD patients were assessed using PUL2.0 and PROM UL. One hundred and twenty-five concurrent PUL 2.0 and PROM UL evaluations from 60 non ambulant DMD boys were taken into consideration. The total PROM UL scores showed a strong correlation with both PUL 2.0 total scores and with PUL 2.0 entry item score. The strong correlation between the two tools confirms the clinical meaningfulness of the PUL2.0 and that the PROM UL can help to detect the gradient of progression of upper limb involvement.

Bulbar and jaw muscles are impaired in patients with Spinal Muscular Atrophy (SMA) but the assessment of their severity and progression are limited by the lack of age-appropriate and disease-specific measures. We investigated mastication and swallowing in children and adults with SMA, sitters and walkers. In a 2-year multicentre cross-sectional prospective study, lip and tongue strength (Iowa Oral Performance Instrument), chewing and swallowing (Test of Masticating and Swallowing Solids), active mouth opening (aMMO) were compared to age-appropriate normative data. The perceived burden of oro-bulbar involvement (SMA-Health Index) was recorded. 78 patients were included, 45 children (median age 7.4 years),22 adults (median age 26.8 years) on nusinersen and 11 untreated (median age 32.7 years). Forty-three percent children had reduced mouth opening, 50% had prolonged total time to eat. These issues were more prominent in sitters than in walkers ( p = 0.019, p = 0.014). Sixty-six percent needed increased swallows for bolus clearance. Nusinersen treated adults had median aMMO, tongue strength and total time at TOMASS values within normal range ( z score: −1.40, −1.22, −1.32, respectively) whereas untreated adults had reduced aMMO ( z score: −2.68) and tongue strength ( z score: −2.20). Only a minority of children (2/17) and treated adults (5/21) reported burden in swallowing or mastication compared to all untreated adults (5/5). After 16 months, mastication and swallowing were stable in treated children and adults, whether sitters or walkers. The reported multimodal approach to assess oro-bulbar functions demonstrate that swallowing and mastication are impaired in SMA despite patients’ perception. These results suggest a trend towards stabilization of oro-bulbar function in patients on long-term treatment with nusinersen.

BACKGROUND:We report the 4-year follow-up in type I patients treated with nusinersen and the changes in motor, respiratory and bulbar function in relation to subtype, age and SMN2 copy number.METHODS:The study included SMA 1 patients with at least one assessment after 12, 24 and 48 months from the first dose of nusinersen. The assessments used were Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the Hammersmith Infant Neurological Examination (HINE-II).RESULTS:Forty-eight patients, with ages ranging from 7 days to 12 years (mean 3.3 years, SD 3.6 years) were included in the study. The CHOP INTEND and HINE-II scores significantly increased between baseline and 48 months (p < 0.001). When age at starting treatment subgroups (<210 days, <2 years, 2-4 years, 5-11 years, ≥12 years) were considered, the CHOP INTEND increased significantly in patients younger than 4 years at treatment, while the HINE-2 increased significantly in patients younger than 2 years at treatment. In a mixed-model analysis, age, nutritional and respiratory status were predictive of changes on both scales while SMN2 copy number and decimal classification were not.CONCLUSIONS:Our results confirm the safety profile previously reported and support the durability of the efficacy of nusinersen at 4 years with an overall stability or mild improvement and no evidence of deterioration over a long period of time.

Background:Efficacy and safety of onasemnogene abeparvovec (OA) for Spinal Muscular Atrophy infants under 7 months and <8.5 kg has been reported in clinical trials. This study examines efficacy and safety predictors in a wide age (22 days-72 months) and weight (3.2-17 kg) range, also including patients previously treated with other drugs. Methods:46 patients were treated for 12 months between January 2020 and March 2022. Safety profile was also available for another 21 patients with at least 6 month follow-up after OA infusion. 19/67 were treatment naïve when treated with OA. Motor function was measured with the CHOP-INTEND. Findings:CHOP-INTEND changes varied among age groups. Baseline score and age at OA treatment best predicted changes. A mixed model post-hoc analysis showed that in patients treated before the age of 24 months the CHOP-INTEND changes were already significant 3 months after OA while in those treated after the age of 24 months the difference was only significant 12 months after OA. Adverse events occurred in 51/67. The risk for elevated transaminases serum levels was higher in older patients. This was also true for weight and for pre-treatment with nusinersen when analysed individually. A binomial negative regression analysis showed that only age at OA treatment had a significant effect on the risk of elevated transaminases. Interpretation:Our paper describes OA 12-month follow-up showing efficacy across various age and weight groups not targeted by clinical trials. The study identifies prognostic factors for safety and efficacy in treatment selection. Funding:None.

INTRODUCTION:The aim of the study was to longitudinally assess swallowing abilities in nusinersen-treated patients with type 1 spinal muscular atrophy.METHODS:Twenty infants with type 1 SMA (11 female and 9 male) treated with nusinersen between 3 weeks and 15 months of age, were assessed using the Oral and Swallowing Abilities Tool (OrSAT). The duration of the follow-up after treatment ranged between 12 months and 62 months.RESULTS:Twelve of the 20 infants had normal swallowing and there was no need for tube feeding at the time treatment started. Ten of the 12 had consistently normal swallowing with no need for tube feeding on follow-up. The other two required tube feeding but they regained the ability to eat some food by mouth.The remaining 8 infants already had tube feeding inserted at the time treatment started: 4 of them also had tracheostomy and they showed no changes on the OrSAT Scale. The other 4 who had tube feeding but no tracheostomy had partial functional improvement.CONCLUSION:Our results suggest that the degree of functional impairment at the time treatment is started can help to predict the progression of swallowing abilities. The use of a structured assessment also helped to detect partial improvements.

The aim of this retrospective study was to review body mass index (BMI) in a large cohort of Italian pediatric type 2 spinal muscular atrophy (SMA) patients, aged between 0 and 20 years and to establish possible differences in relation to a number of variables such as ventilation, motor function, and survival motor neuron 2 gene copies. Cross-sectional data were collected from 102 patients for a total of 344 visits. Standard growth charts for height and weight were used as reference, with age adjusted BMI calculated using the Center for Disease and Prevention Children’s BMI Tool. In the 344 visits, weight ranged between 3.90 and 83 kg, and the BMI between 8.4 and 31.6 with a BMI/age z -scores < − 2SD present in 28% and BMI/age z -scores > + 2SD in 9% of the measurements. The BMI/age z -scores were relatively stable < 5 years of age with an increasing number of patients < − 2SD after the age of 5, and a wider range of BMI/age z -scores after the age of 13. A difference on the BMI/age z -scores was found among the different age subgroups (< 5, 5–12, ≥ 13 years). A multivariate analysis in 58 patients with longitudinal assessments showed that baseline BMI/age z -scores and gender were significantly contributing to the changes while other variables were not. Conclusion : Our results confirm that careful surveillance of weight and BMI/age z -scores is needed in type 2 SMA. Further studies, including assessments of chewing and swallowing and of lean/fat body mass, will help to better understand the possible mechanisms underlying weight issues. What is Known: • Feeding difficulties have been reported in a few studies and were invariably found in patients with type 1 SMA. • Type 2 SMA patients often have low BMI with a relevant number of patients requiring tube feeding. What is New: • Reduction in BMI/age z-score overtime appeared to depend on baseline BMI/age z-score and gender. • Patients with a low BMI/age z-score were at higher risk of developing further reduction.

The possibility to identify patients with spinal muscular atrophy through neonatal screenings has highlighted the need for clinical assessments that may systematically evaluate the possible presence of early neurological signs. The aim of this study was to use the Hammersmith Neonatal Neurological Examination (HNNE) and a module specifically designed for floppy infants to assess the possible variability of neurological findings in infants identified through neonatal screening. The infants included in this study were identified as part of a pilot study exploring neonatal screening in two Italian regions. A neurological examination was performed using the HNNE and an additional module developed for the assessment of floppy infants. Seventeen infants were identified through the screening. One patient had 1 SMN2 copy, 9 had 2 copies, 3 had 3, and 4 had more than 3 copies. Nine of the 17 infants (53%) had completely normal results on both scales, 3 had minimal signs, and the other 5 had more obvious clinical signs. The number of SMN2 copies was related to the presence of abnormal neurological signs (p = 0.036) but two SMN2 copies were associated with variable clinical signs as they were found in some infants with respectively normal examination or obvious severe early signs. Conclusions: Our results suggest that the combination of both scales increases the possibility to detect neonatal neurological signs and to define different early patterns of involvement also identifying paucisymptomatic patients.

Spinal muscular atrophy with respiratory distress type 1 (SMARD1, OMIM #604,320), is a rare autosomal recessive disease resulting from degeneration of motor neurons in the anterior horns, which leads irreversible diaphragmatic palsy and progressive distal symmetrical muscular weakness. Respiratory distress is the main symptom and is severe, rapidly progressive, and frequently requiring invasive ventilation. Despite diaphragm being one of the target organ of the disease, no specific study has been done using ultrasound.We report diaphragm and lung ultrasound findings of a 13-month-old girl affected by SMARD1 (homozygosis c.1540G > A mutation in IGHMPB2 gene) with respiratory failure requiring permanent mechanical ventilation since birth and we discuss the role of diaphragmatic and lung ultrasound in this category of patients and its clinical implications.

Abstract Objective The aim of this paper was to report the 2‐year follow‐up in type I patients treated with Nusinersen and to assess whether possible changes in motor function are related to the subtype, age, or SMN2 copy number. Methods Sixty‐eight patients, with ages ranging from 0.20 to 15.92 years (mean: 3.96; standard deviation: +3.90) were enrolled in the study. All patients were assessed using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the developmental section of the Hammersmith Infant Neurological Examination (HINE‐2) at the time they started treatment and 12 and 24 months after that. Results For both CHOP and HINE‐2 repeated measures analysis of variance showed a significant difference (P < 0.001) between baseline and 12 months, 12 months and 24 months, and baseline and 24‐month scores for the whole group. When age subgroups (<210 days, <2 years, 2–4 years, 5–11 years, 12–18 years) were considered, on the CHOP INTEND the difference was significant between baseline and 24 months in all age subgroups. On the HINE‐2, the difference between baseline and 24 months was significant in all the subgroups before the age of 4 years. Age was predictive of changes on both scales (P < 0.05), whereas SMN2 copy number and decimal classification were not. Interpretation Our results suggest that some improvement of motor function can be observed even after the first year of treatment. This is more obvious in the infants treated in the first 2 years but some improvement can also be found in older children.