Spinal Muscular Atrophy Children Research Articles

Clinical efficacy of nusinersen sodium in the treatment of children with spinal muscular atrophy

To investigate the efficacy and safety of nusinersen sodium in the treatment of children with spinal muscular atrophy (SMA). A retrospective analysis was conducted on the clinical data of 50 children with 5q SMA who received nusinersen sodium treatment and multidisciplinary treatment management in Shanxi Children's Hospital from February 2022 to February 2024. Compared with the baseline data, 67% (8/12), 74% (35/47), and 74% (35/47) of the SMA children had a clinically significant improvement in the scores of Philadelphia Infant Test of Neuromuscular Disorders, Hammersmith Functional Motor Scale Expanded, and Revised Upper Limb Module, respectively, and the distance of 6-minute walking test increased from 207.00 (179.00, 281.50) meters to 233.00 (205.25, 287.50) meters (P<0.05) after nusinersen sodium treatment. Of all 50 children with SMA, 24 (48%) showed good tolerability after administration, with no significant or persistent abnormalities observed in 2 034 laboratory test results, and furthermore, there were no serious or immunological adverse events related to the treatment. After treatment, there was a significant change in forced vital capacity as a percentage of the predicted value in 27 children with restrictive ventilatory dysfunction, as well as a significant change in the level of 25-(OH) vitamin D in 15 children with vitamin D deficiency (P<0.05). For children with SMA, treatment with nusinersen sodium can continuously improve the response rates of motor function scales, with good tolerability and safety.

Real-World Safety Data of the Orphan Drug Onasemnogene Abeparvovec (Zolgensma®) for the SMA Rare Disease: A Pharmacovigilance Study Based on the EMA Adverse Event Reporting System.

The recent introduction of the innovative therapy, onasemnogene abeparvovec (Zolgensma®), has revolutionized the spinal muscular atrophy (SMA) therapeutic landscape. Although Zolgensma® therapy has proven to lead to functional improvements in SMA children, some gaps in its safety profile still need to be investigated. To better characterize the Zolgensma® safety profile, we conducted a retrospective observational study, analyzing all the Individual Case Safety Reports (ICSRs) referred to it and collected in the European pharmacovigilance database between 1 January 2019 and 22 September 2023. We found 661 ICSRs related to Zolgensma®, with a growing trend in the annual reporting. The majority of the reports were sent by healthcare professionals and referred to infant females. In more than 90% of the cases, Zolgensma® was the only reported suspected drug. Out of a total of 2744 reported ADRs, increased hepatic enzymes, pyrexia, vomiting, and thrombocytopenia were the most commonly reported adverse reactions. Of these adverse reactions (ADRs), 56.9% were serious, causing or prolonging the patient's hospitalization. A total of 39 ICSRs related to cases with a fatal outcome. Alterations in the heart rhythm, acute hepatic failure, and hepatic cytolysis emerged among the cardiac and hepatic disorders, respectively.

Cardiac function evaluation in children with spinal muscular atrophy: A case-control study.

Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by degeneration of lower motor neurons, resulting in progressive muscle weakness and atrophy. However, little is known regarding the cardiac function of children with SMA. We recruited SMA patients younger than 18 years of age from January 1, 2022, to April 1, 2022, in the First Affiliated Hospital of Sun Yat-sen University. All patients underwent a comprehensive cardiac evaluation before treatment, including history taking, physical examination, blood tests of cardiac biomarkers, assessment of echocardiography and electrocardiogram. Age/gender-matched healthy volunteers were recruited as controls. A total of 36 SMA patients (26 with SMA type 2 and 10 with SMA type 3) and 40 controls were enrolled in the study. No patient was clinically diagnosed with heart failure. Blood tests showed elevated values of creatine kinase isoenzyme M and isoenzyme B (CK-MB) mass and high-sensitivity cardiac troponin T (hs-cTnT) in spinal muscular atrophy (SMA) patients. Regarding echocardiographic parameters, SMA children were detected with lower global left and right ventricular longitudinal strain, abnormal diastolic filling velocities of trans-mitral and trans-tricuspid flow. The results revealed no clinical heart dysfunction in SMA patients, but subclinical ventricular dysfunction was seen in SMA children including the diastolic function and myocardial performance. Some patients presented with elevated heart rate and abnormal echogenicity of aortic valve or wall. Among these SMA patients, seven patients (19.4%) had scoliosis. The Cobb's angles showed a significant negative correlation with LVEDd/BSA, but no correlation with other parameters, suggesting that mild scoliosis did not lead to significant cardiac dysfunction. Our findings warrant increased attention to the cardiac status and highlight the need to investigate cardiac interventions in SMA children.

Efficacy and safety of salbutamol in treatment of children with later-onset spinal muscular atrophy.

To investigate the clinical efficacy and safety of salbutamol in the treatment of children with later-onset spinal muscular atrophy (SMA). This study is a prospective single-arm phase Ⅲ clinical study. Pediatric patients with SMA type Ⅱ and Ⅲ who visited Department of Neurology, Children's Hospital, Zhejiang University School of Medicine from December 2020 to June 2022 were enrolled. All patients were evaluated with motor function scales, pulmonary function test and drug safety before study. Patients were treated with salbutamol tablets orally, with an initial dose of 1 mg (tid). If tolerable, the dose was increased to 1.5 mg (tid) in the second week, then increased to 2 mg (tid) from the third week and maintained for 6 months. Patients were followed up at 1, 3 and 6 months of treatment. Twenty-six patients were enrolled, including 10 boys and 16 girls. There were 16 cases of SMA type Ⅱ and 10 cases of type Ⅲ with age at treatment initiation of 5.67 (3.13, 7.02) years and disease duration of 2.54 (1.31, 4.71) years. The Hammersmith Functional Motor Scale-Expanded (HFMSE) scores were increased from 14.0 (6.5, 43.0) before treatment to 26.0 (15.0, 46.5) after treatment (Z=－4.144, P<0.01) in 25 cases. The Revised Upper Limb Module Scale scores were increased from 33.0 (25.5, 36.0) before treatment to 35.0 (31.0, 36.5) after treatment (Z=－2.214, P<0.05) in 9 cases. In 7 ambulant children with SMA type Ⅲ, the six minutes walking distance was increased by 30 (15, 52) m after a 6-month treatment (Z=－2.366, P<0.05). Compared with the baseline pulmonary functions the patients showed a significant increase in forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF) in 15 cases after treatment (all P<0.05). According to patients and caregivers subjective reporting, there were various degrees of improvement in coughing, sputum production ability and exercise endurance. No serious adverse events were observed during the study. Short-term oral administration of salbutamol may improve motor and pulmonary functions in later-onset SMA children with good safety.

Asymptomatic troponin I elevation and acute myocarditis in the late period of gene replacement therapy with onasemnogene aberpavovec for patients with spinal muscular atrophy: literature review and clinical case series

Introduction. Spinal muscular atrophy (SMA) 5q is a rare genetically determined progressive neuromuscular disorder, is the most frequent cause of infant death not long ago. Nowadays onasemnogen abeparvovec as pathogenetic therapy is successfully used in clinical practice to combat this disease. Gene replacement therapy (GRT) with onasemnogen abeparvovec for SMA patients may come amid non-target changes in the cardiovascular system that require early diagnosis and monitoring.&#x0D; Objective. To present clinical reports considering children with genetically confirmed SMA and elevated troponin I levels after onasemnogen abeparvovec gene replacement therapy.&#x0D; Materials and methods. We monitored forty two children with genetically confirmed SMA who received gene replacement therapy with onasemnogen abeparvovec in the pediatric neurology department. All patients were tested for troponin I before and after the infusion, additional tests of N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP), creatine phosphokinase-MB (CPK-MB), electrocardiogram, echocardiography were made if needed.&#x0D; Results. In 11 (26.2%) of 42 SMA children troponin I was elevated and detected up to the eighth week after drug administration. At the same time, an increased concentration of troponin I in the majority of cases (41 out of 42 children) was not associated with clinically significant manifestations. There was only one case when acute myocarditis, confirmed by clinical and instrumental methods of investigation occurred. It was a girl with a long-term (10 months) elevation of troponin I, who had an intercurrent infection.&#x0D; Conclusions. Troponin I elevations detected after GRT with onasomnogene abeparvovec in SMA patients are often asymptomatic. This myocarditis case highlights the importance of longer cardiac monitoring of troponin I elevations, especially in the presence of intercurrent bacterial and viral infections.

Identifying Clinical and Genetic Characteristics of Spinal Muscular Atrophy Patients and Families in Saudi Arabia.

Spinal muscular atrophy (SMA) is an inherited, neuromuscular disease characterized by the deterioration of spinal motor neurons, causing progressive muscular atrophyand weakening. It is an autosomal recessive disease with the mutation of the survival motor neuron 1 (SMN1) gene as a hallmark. Evidence suggests that the SMN2 gene modulates the severity of the disease. SMA is classified based on the maximum motor function achieved. This study aims to describe the genetic makeup and characteristics of an SMA cohort in the Kingdom of Saudi Arabia (KSA). Data from families presenting with SMA children was collected between January 2018 and December 2020. Blood samples were collected from patients and family members. Genetic testing for SMA and mutations was performed at a European central lab. Seventeen families were enrolled in the study, including 52 children. Among 34 parents, 28 were carriers with heterozygous deletion (82.3%), one (2.9%) had no deletion detected by multiplex ligation-dependent probe amplification (MLPA) but had point mutation by sequencing, one (2.9%) had homozygous deletion and was symptomatic, three (8.8%) had no deletion or point mutation and were presumed to have 2+0, and one (2.9%) was not tested. This study provides insight into the carrier mutational analysis of families with SMA disease manifestations in KSA. Further studies are needed to understand the burden and impact of SMA among the Saudi population.

Feasibility analysis of intrathecal administration strategy of nusinersen based on Cobb angle in children with spinal muscular atrophy.

This retro-prospective observational study described the experience in lumbar puncture procedures in children with spinal muscular atrophy (SMA) with and without neuromuscular scoliosis in a single center. The technical feasibility of intrathecal nusinersen administration was the main limiting factor. A total of 457 technically successful intrathecal injections based on a hierarchical strategy in Cobb angle were reviewed in 81 SMA children aged 0.75-13.5 years who were referred for nusinersen injections in our hospital from October 2019 to December 2022. Under local anesthesia, conventional lumbar puncture was performed on 47 patients without spinal deformity (Cobb angle of 0-10°) and 20 patients with moderate scoliosis (Cobb angle of 10-50°). Ultrasound-assisted lumbar puncture was performed on 12 patients with moderate scoliosis but lordosis. A combination of ultrasound imaging and three-dimensional CT under sedation was performed in the remaining 14 patients with severe scoliosis (Cobb angle >50°). No severe complications were found. Cobb angle is an important basis for intrathecal administration of nusinersen. It is feasible and suitable to carry out intrathecal nusinersen injection under ultrasound combined with three-dimensional CT imaging for children with severe scoliosis.

Influence of Paraspinal Growth-Friendly Spinal Implants in Children with Spinal Muscular Atrophy on Parasol Deformity, Rib-Vertebral Angles, Thoracic, and Lung Volumes

Introduction: Children with spinal muscular atrophy (SMA) and progressive neuromuscular scoliosis often require early growth-friendly spinal implant (GFSI) treatment for deformity correction with implant fixation either through pedicle screws or bilateral to the spine using ribto pelvis fixation. It has been proposed that the latter fixation may change the collapsing parasol deformity via changes in the rib-vertebral angle (RVA) with a positive effect on thoracic and lung volume. The purpose of this study was to analyze the effect of paraspinal GFSI with bilateral rib-to-pelvis fixation on the parasol deformity, RVA, thoracic, and lung volumes. Methods: SMA children with (n = 19) and without (n = 18) GFSI treatment were included. Last follow-up was before definite spinal fusion at puberty. Scoliosis and kyphosis angles, parasol deformity, and index, as well as convex and concave RVA, were measured on radiographs, whereas computed tomography images were used to reconstruct thoracic and lung volumes. Results: In all SMA children (n = 37; with or without GFSI), convex RVA was smaller than concave values at all times. GFSI did not crucially influence the RVA over the 4.6-year follow-up period. Comparing age- and disease-matched adolescents with and without prior GFSI, no effect of GFSI treatment could be detected on either RVA, thoracic, or lung volumes. Parasol deformity progressed over time despite GFSI. Conclusion: Despite different expectations, implantation of GFSI with bilateral rib-to-pelvis fixation did not positively influence parasol deformity, RVA and/or thoracic, and lung volumes in SMA children with spinal deformity directly and over time.

Early Development of Spinal Deformities in Children Severely Affected with Spinal Muscular Atrophy after Gene Therapy with Onasemnogene Abeparvovec-Preliminary Results.

Spinal muscular atrophy (SMA) is a rare genetic disorder, with the most common form being 5q SMA. Survival of children with severe SMA is poor, yet major advances have been made in recent years in pharmaceutical treatment, such as gene-therapy, which has improved patient survival. Therefore, clinical problems, such as the development of spinal deformities in these genetically treated SMA children represent an unknown challenge in clinical work. In a retrospective case series, the development of spinal deformities was analyzed in 16 SMA children (9 male, 7 female) treated with onasemnogene abeparvovec in two institutions during the years 2020 to 2022. Ten out of sixteen patients had a significant kyphosis, and nine out of sixteen patients had significant scoliosis, with the mean curvature angles of 24 ± 27° for scoliosis, and 69 ± 15° for kyphosis. Based on these preliminary data, it can be assumed that early-onset kyphosis presents a clinical challenge in gene-therapy-treated SMA children. Larger datasets with longer follow-up times need to be collected in order to verify these preliminary observations.

Scoliosis Treatment With Growth-Friendly Spinal Implants (GFSI) Relates to Low Bone Mineral Mass in Children With Spinal Muscular Atrophy.

Children with spinal muscular atrophy (SMA) frequently develop neuromuscular scoliosis at an early age, requiring surgical treatment with growth-friendly spinal implants (GFSI), such as magnetically controlled growing rods. This study investigated the effect of GFSI on the volumetric bone mineral density (vBMD) of the spine in SMA children. Seventeen children (age 13.2±1.2 y) with SMA and GFSI-treated spinal deformity were compared with 25 scoliotic SMA children (age 12.9±1.7 y) without prior surgical treatment as well as age-matched healthy controls (n=29; age 13.3±2.0). Clinical, radiologic, and demographic data were analyzed. For the calculation of the vBMD Z-scores of the thoracic and lumbar vertebrae, phantom precalibrated spinal computed tomography scans were analyzed using quantitative computed tomography (QCT). Average vBMD was lower in SMA patients with GFSI (82.1±8.4 mg/cm 3) compared with those without prior treatment (108.0±6.8 mg/cm 3 ). The difference was more prominent in and around the thoracolumbar region. The vBMD of all SMA patients was significantly lower in comparison with healthy controls, especially in SMA patients with previous fragility fractures. The results of this study support the hypothesis of reduced vertebral bone mineral mass in SMA children with scoliosis at the end of GFSI treatment in comparison with SMA patients undergoing primary spinal fusion. Improving vBMD through pharmaceutical therapy in SMA patients could have a beneficial effect on the surgical outcome of scoliosis correction while reducing complications. Therapeutic Level III.

Respiratory and sleep outcomes in children with SMA treated with nusinersen - real world experience

It is unclear how improvements in peripheral motor function in children with spinal muscular atrophy (SMA), treated with nusinersen, translate into clinically significant respiratory/sleep outcomes. A retrospective chart review of SMA children at the Sydney Children's Hospital Network was undertaken looking at 2 years before and after receiving their first dose of nusinersen. Polysomnography (PSG), spirometry and clinical data were collected and analysed using paired and unpaired t-tests for PSG parameters and generalised estimating equations for longitudinal lung function data. Forty-eight children (10 Type 1, 23 Type 2, 15 Type 3) at mean age 6.98 yrs (SD 5.25) for nusinersen initiation were included. There was a statistically significant improvement in oxygen nadir during sleep in individuals post nusinersen (mean of 87.9% to 92.3% (95%CI 1.24 – 7.63, p = 0.01)). Based on clinical and PSG findings, 6/21 patients (5 Type 2, 1 Type 3) ceased nocturnal NIV post nusinersen. Non-significant improvements were demonstrated in mean slope for FVC% predicted, FVC Z-score and mean FVC% predicted. Within 2 years of commencing nusinersen, stabilisation of respiratory outcomes occurred. Whilst some of the SMA type 2/3 cohort ceased NIV, there were no statistically significant improvements lung function and most PSG parameters.

Behavioral problems in infants and young children with spinal muscular atrophy and their siblings: A cross-sectional study.

Older children and adults with spinal muscular atrophy (SMA) have been shown to have more anxiety, depression, and other behavioral problems in a few studies. But no similar studies have been performed in infants and young children with SMA. Behavioral co-morbidities of young children with SMA were compared with healthy and children with chronic non-neurological illness control group. Infant Behavior Questionnaire-Revised (IBQ-R) and parent-report version of chid behavior checklist (CBCL) were used for infants and preschool-age children respectively. A total of 35 SMA children (age at symptom onset-5.9±2.8 months, at enrolment-21.4±7.1 months, 65% boys, 11, 19 and 5 were SMA 1, 2 and 3 respectively) and 24 siblings (38.6±11.2 months, 71% boys) were enrolled. We also enrolled 15 children with nephrotic syndrome as age and gender matched control to SMA children in age-group 2-5 years (27.7±9.1 months, 67% boys). In infants with SMA, the scale scores of IBQ-R were significantly higher for distress to limitation, fear, sadness, and falling reactivity/rate of recovery from distress (p=0.005; 0.03; 0.001, and 0.04) and lower for soothability as compared to healthy control group (p=0.04). Similarly, for the three dimensions of temperament computed from these 13 domains, the mean scale score for surgency/extraversion was lower and negative affectivity was higher (p=0.04 and 0.03), in infants with SMA as compared to healthy controls. For preschool age group, the internalizing problem scores (p=0.009 and 0.03) and stress problem scores (p=0.002 and 0.04) were higher in the SMA group, as compared to both the healthy control group and diseased control group. While assessing the syndrome scale scores, the score was higher for emotionally reactive (p=0.0002 and 0.01) and anxious domains (p<0.0001 and p=0.0002) compared to both healthy and diseased control groups. Infants and young children with SMA suffer from increased internalizing problems like anxiety, depression and probably their healthy siblings are also at increased levels of stress, depicted by increased somatic complaints.

The quality of life in children with spinal muscular atrophy: a case–control study

ObjectivesThis study aimed to analyze the health-related quality of life (HRQoL) of patients with spinal muscular atrophy (SMA) based on the type of SMA, demographic and clinical features and compare HRQoL of these patients with a matched healthy control group. MethodsThis was a case–control study of Patients with SMA in Iran. Sixty-six patients with SMA type II and III aged 8–18 years and also 264 healthy age, sex, and socio-economic matched individuals were enrolled. To assess the quality of life, we used the Persian version of the KIDSCREEN-27.ResultsThe health-related quality of life between children with type II and type III SMA was not significant in all 5 subscales. However, HRQoL in healthy children was significantly higher than in SMA children in all 5 subscales.ConclusionThe quality of life in children with SMA was lower than the healthy control group in all subscales, and physical well-being and psychosocial aspects are the main domains of life impaired by SMA disease. However, no significant difference between the quality of life in children with SMA type II and type III was observed.

Analysis of scores of Symptom Checklist 90 (SCL-90) questionnaire of 182 parents of children with spinal muscular atrophy: a cross-sectional study.

Spinal muscular atrophy (SMA) is a hereditary disorder characterized by progressive muscle weakness and atrophy in children. However, less attention is paid to psychiatric symptoms of SMA parents. Attention to the psychiatric symptoms of parents of SMA children can improve the comprehensiveness of family support for SMA children, which is beneficial to the rehabilitation of SMA children. Here, we conducted a survey on the psychiatric symptoms of SMA parents and analyzed its relevant factors, with an attempt to inform the psychological support for SMA parents. The Symptom Checklist 90 (SCL-90) and a self-designed basic information (such as parent's gender, household area, place of residence, education background, etc.) questionnaire (in electronic questionnaire) were distributed to parents of SMA children aged 0-18 in a charity WeChat group sponsored by the Meier Advocacy & Support Center for SMA during the period from August 1 to August 31, 2021. Parents completed the electronic questionnaires by mobile phone or computer voluntarily. A total of 188 questionnaires were obtained, of which 182 were valid. Comparisons were performed with the SCL-90 adult norms as the standards. The potential correlations between the general data of SMA parents and children and abnormal factors in the SCL-90 for SMA parents were analyzed. The SCL-90 factors somatization (1.56±0.80, P=0.002), depression (1.78±0.98, P<0.001), anxiety (1.58±0.87, P=0.007), fear (1.39±0.74, P=0.003), and sleep and eating problems (1.67±0.87, P=0.014) of SMA parents were significantly higher than the national norms. Place of residence was correlated with sleep and eating problems (r=0.158, P=0.033). Increasing age [odds ratio (OR) =1.012, P=0.014] and continuous home-living status (OR =0.360, P=0.031) of SMA children increased the risk of depression in their parents, and the lack of rehabilitation management in SMA children increased the risk of anxiety of their parents (OR =0.409, P=0.038). Non-urban residence (OR =2.602, P=0.017) and poor physical health (OR =0.163, P=0.031) were the relevant factors for the increased risk of sleep and eating problems in SMA parents. SMA parents have a higher risk of developing psychiatric symptoms problems compared with the general population. Increasing age and the continuous home-living status of SMA children increase the risk of depression in their parents, and the lack of rehabilitation management increase the risk of anxiety in SMA parents.

VP.14 Growth patterns in treated SMA children in the UK

Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by degeneration of alpha motor neurons in the spinal cord. SMA type 1 (SMA1) is the most severe form, with patients never achieving sitting, whilst patients with SMA type 2 (SMA2) are sitters who are not able to walk independently. Disease modifying treatments such as nusinersen, onasemnogene abeparvovec, and risdiplam have led to increases in motor function and life expectancy. However, not much is known about the effect of these treatments on growth. The aim of this retrospective study was to analyse the patterns in weight, height, and BMI of treated SMA1 and SMA2 patients compared with the UK90 reference population. Cross-sectional data on growth was obtained from the SMA Research and Clinical Hub UK (SMA REACH UK) national database. Results are based on last available measurements of SMA1 (n=57) and SMA2 (n=41) nusinersen treated children. Median age was 3.02 (IQR: 1.44-4.78), and 6.93 (IQR: 4.73-8.81) years for SMA1 and SMA2, respectively. The results showed that compared to the paediatric normative data, SMA1 and SMA2 had a lower weight with the median weight z-score of -0.96 (IQR: -1.97; -0.16) and -1.20 (IQR: -2.02; 0.16), respectively. SMA2 children presented with a lower median height z-score (-1.37 (IQR: -2.19; -0.22)), compared to those with SMA1 (-0.91 (IQR: -2.28; 0.83)). Consequently, median BMI z-score was -0.90 (IQR: -2.82; 0.80) for SMA 1, and -0.63 (IQR: -1.46; 1.45) for SMA2 patients. Approximately a quarter of the children in this group are considered underweight (Weight SD score <=-2) for both SMA1 (25%) and SMA2 (27%). Children with SMA2 are more likely to be overweight (BMI SD score >=2) than patients with SMA1, with rates of 15% and 4% respectively. This analysis sheds light on how growth is affected by novel disease modifying treatments in SMA.

The alteration of left ventricular strain in later-onset spinal muscular atrophy children.

BackgroundPatients with spinal muscular atrophy (SMA) may suffer from multisystem injury, including an impaired cardiovascular system. However, M-mode echocardiography, the current dominant echocardiographic modality, is limited in the detection of myocardial injury. We considered the use of left ventricular strain imaging in detecting myocardial injury and explored the serum lipid profile related to cardiovascular disease in later-onset SMA children.MethodsA case-control study involving 80 patients with later-onset SMA and 80 age-, gender-, and body surface area-matched control children was conducted in a single tertiary pediatric hospital in China. Data on the left ventricular strain measured using two-dimensional speckle tracking echocardiography, left ventricular function parameters assessed by M-mode echocardiography, and serum lipid profile of these two groups were retrospectively collected for differential analysis.ResultsThe mean age of the 80 SMA patients were (6.87 ± 2.87) years, of which 46 were type 2 and 34 were type 3 patients. The global longitudinal strain (GLS) of the SMA group (−18.7 ± 2.9%, p < 0.001) was lower than that of the control group; the time to peak longitudinal strain (TTPLS) of the SMA group (22.9 ± 13.6 ms, p < 0.001) was higher than that of the control group, while left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), measured by the Teichholz method of M-mode echocardiography, showed no significant differences between the two groups. In addition, independent indicators for cardiovascular risk, including total cholesterol (TC)/HDL, low-density lipoprotein (LDL)/HDL, and Apo B/Apo A1 levels, were higher in SMA children than in the control group.ConclusionCompared with healthy controls, later-onset SMA children presented with reduced GLS and prolonged TTPLS while the LVEF and LVFS values were within normal range. In particular, whether a reduced GLS or prolonged TTPLS in later-onset SMA compared to the control group can predict the risk of future cardiomyopathy remains to be investigated.

Health-related quality of life in Thai children with spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a chronic genetic disease that causes varying degrees of disability. There is currently no data specific to the health-related quality of life (HRQoL) of Thai children and adolescents with SMA. Accordingly, this study aimed to evaluate the HRQoL of Thai pediatric SMA, and to identify factors significantly associated with HRQoL and other aspects of quality of life. The findings of this study will help to improve overall care in this vulnerable pediatric population. This prospective cross-sectional descriptive study was conducted at the Division of Neurology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand during 2015-2018. HRQoL was measured using the Thai language version of the Pediatric Quality of Life Inventory™ 4.0 Generic Core Scale (PedsQL™). The PedsQL™ was administered to SMA children aged 2-18 years and their parents. Disease severity was evaluated by pediatric neurologists, and patients were classified according to their SMA subtype. Forty-two Thai pediatric SMA (mean age: 9.8±5.0 years, 25 males) and their families were recruited. The mean PedsQL™ total score was 57.3±13.6 by child self-report, and 54.3±14.8 by parent proxy-report. The PedsQL™ scores of Thai SMA children were found to be significantly lower than those reported in healthy Thai children. The mean PedsQL™ total score among healthy Thai children was 78.7±9.3 by child self-report, and 79.0±12.8 by parent proxy-report. Factors independently associated with lower HRQoL were non-ambulation, household income less than 18,500 Thai baht/month, mechanical ventilation, and inability to attend school. HRQoL score was found to be an accurate reflection of patient and parent perception of SMA, which suggests the value of this tool for prioritizing interventions to improve the quality of life of Thai SMA. The results of this study also provide a baseline measurement of quality of life among Thai SMA.

Safety profile of onasemnogene abeparvovec in children with spinal muscular atrophy

Goal. To evaluate the safety profile of onasemnogene abeparvovec (Zolgensma®) gene therapy in children with spinal muscular atrophy (SMA) in real clinical practice. Materials and methods. The study included 30 SMA children who underwent gene replacement therapy with onasemnogene abeparvovec (Zolgensma®) from December 2020 to December 2021 at the Center for Pediatric Psychoneurology. All children had a diagnosis of SMA confirmed by molecular genetic methods, with no more than 3 copies of the SMN2 gene and the absence of antibodies to the adeno-associated virus serotype 9. The safety profile was assessed by monitoring the clinical and laboratory data of the patients after administration of onasemnogene abeparvovec. Clinical events included all changes in the child’s condition that could be associated with the administration of the drug (hyperthermia, decreased appetite, nausea, vomiting, stool disorders). Laboratory assessment included monitoring of complete blood count, biochemical blood tests, blood coagulation indices. The degree of laboratory changes was estimated according to common terminology criteria for adverse events (CTCAE version 5.0). Results. The safety profile of the drug Zolgensma® was studied in 30 children aged from 3 to 39 months, with a weight of 5.2 kg to 14.2 kg. Twenty-eight (93.3%) children had at least one clinical event associated with the administration of the drug. Hyperthermia was observed in 24 (80%) children, nausea and vomiting in 18 (60%) children, decreased appetite in 20 (66.7%) children, stool changes in 4 (13.3%) children. Monitoring of laboratory indices revealed thrombocytopenia and monocytosis in twenty-two (73.3%) children and neutropenia in twelve (40%) children in the general blood test. An increase in the level of transaminases was noted in all children, the CTCAE grade 1 was detected in fifteen (50%) children, the CTCAE grade 2 in 7 (23.3%) children, CTCAE grade 3 in 6 (20%) children, CTCAE grade 4 in 2 (6.7%) children. Children with CTCAE grade 3 required correction of the prednisone dose up 2 mg/kg per day for 2-4 weeks. Two children with CTCAE grade 4 required pulse therapy with methylprednisolone at a dose of 30 mg/kg per day. Regardless of the level of transaminases, no change in the level of total and direct bilirubin was observed in any case. A decrease in prothrombin time was observed in 14 (46.6%) children. An increase in the level of troponin I was detected in four (13.3%) children. In all cases of serious adverse events, according to laboratory indices, the clinical condition of the children remained stable. The average duration of prednisone intake was 17.8 ± 6.6 weeks. Conclusion. The safety profile of the drug onasemnogene abeparvovec (Zolgensma®) in real clinical practice in children with SMA is presented.

Gait-assisted exoskeletons for children with cerebral palsy or spinal muscular atrophy: A systematic review.

Cerebral Palsy (CP) and Spinal Muscular Atrophy (SMA) are common causes of motor disability in childhood. Gait exoskeletons are currently being used as part of rehabilitation for children with walking difficulties. To assess the safety and efficacy and describe the main characteristics of the clinical articles using robot-assisted gait training (RAGT) with exoskeleton for children with CP or SMA. A computer search was conducted in five bibliographic databases regarding clinical studies published in the last ten years. In order to be included in this review for further analysis, the studies had to meet the following criteria: (1) assess efficacy or safety of interventions; (2) population had to be children with CP or SMA aged between 3 and 14; (3) exoskeleton must be bilateral and assist lower limbs during walking. Twenty-one articles were selected, of which only five were clinical trials. 108 participants met the inclusion criteria for this study, all with a diagnosis of CP. The evidence level of the selected papers was commonly low. RAGT therapy seems to be safe for children with CP. However, further investigation is needed to confirm the results related to efficacy. There is no evidence of RAGT therapy for SMA children.

Natural history of spinal muscular atrophy in children: an analysis of 117 cases.

To study the natural history of spinal muscular atrophy (SMA) in Chongqing and surrounding areas, China, and to provide a clinical basis for comprehensive management and gene modification therapy for SMA. A retrospective analysis was performed on the medical data and survival status of 117 children with SMA. Of the 117 children, 62 (53.0%) had type 1 SMA, 45 (38.5%) had type 2 SMA, and 10 (8.5%) had type 3 SMA, with a median age of onset of 2 months, 10 months, and 15 months, respectively. Compared with the children with type 2 SMA or type 3 SMA, the children with type 1 SMA had significantly shorter time to onset, consultation, and confirmed diagnosis (P<0.05) and a significantly shorter diagnostic time window (age from disease onset to consultation) (P<0.05). Pneumonia as the initial symptom, weakness in head control, crying weakness, and eating difficulty were more commonly observed in children with type 1 SMA (P<0.05). Scoliosis and lower limb joint contracture were more common in children with type 2 SMA than in those with type 1 SMA (P<0.05). All 117 SMA children (100%) had homozygous deletion of the SMN1 gene, and the homozygous deletion of exon 7 was the most common type (68.4%, 80/117). The 6-year survival rate of children with type 1 SMA was only 10%±5%, which was significantly lower than that of children with type 2 or 3 SMA (P<0.05). Age of onset ≤3 months, pneumonia as the initial symptom and weakness in head control were the risk factors for death in children with type 1 SMA (P<0.05). The children with type 2 SMA had non-linear regression of motor ability. There are differences in clinical manifestations and survival rates among children with different types of SMA. The children with type 1 SMA have a low survival rate, and those with type 2 SMA may have non-linear regression of motor ability. Early identification and management of SMA should be performed in clinical practice.