Changes in Ventilatory Support Requirements of Spinal Muscular Atrophy (SMA) Patients Post Gene-Based Therapies

Panagiotou, Panagiota; Kanaka‐Gantenbein, Christina; Kaditis, Athanasios G.

doi:10.3390/children9081207

Cited by 8 publications

(3 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent retrospective cohort study of children with SMA1 who initiated nusinersen at a median age of 42.8 months found that only 9 of 109 children did not require NIV 300 days after the first infusion 7 . No children in our study were weaned off ventilatory support during the study period, which was aligned with the results of a recent review reporting similar findings 30 . Although respiratory disease may not be completely reversed by treatment with nusinersen, it is clear that nusinersen treatment attenuates the natural trajectory of rapidly progressive chronic respiratory failure.…”

Section: Discussionsupporting

confidence: 90%

Respiratory characteristics in children with spinal muscular atrophy type 1 receiving nusinersen

Xiao

Chiang

Castro‐Codesal

et al. 2022

Pediatric Pulmonology

View full text Add to dashboard Cite

Background: Spinal muscular atrophy type 1 (SMA1) is a neuromuscular disorder with a natural history of chronic respiratory failure and death during infancy without ventilation. Recently, disease-modifying therapies such as nusinersen have improved disease trajectory. However, objective data on the trajectory of polysomnography outcomes, the relationship between motor scores and respiratory parameters, respiratory technology dependence and healthcare utilization in children with SMA1 remain to be elucidated. Methods: This was a retrospective observational study of children with SMA1 receiving nusinersen between October 2016 and February 2021 at two tertiary care hospitals in Canada. Baseline polysomnography data, motor scores, respiratory technology, and unanticipated healthcare utilization were examined. Results: Eleven children (five females, two SMN2 copies each) were included. Median (interquartile range [IQR]) age at diagnosis was 3.6 (2.8-5.0) months and age at diagnostic polysomnogram following nusinersen initiation was 9.4 (5.3-14.0) months. Nusinersen was initiated at a median (IQR) age of 5.4 (3.4-7.6) months and 8/11 children had respiratory symptoms at that time. Diagnostic polysomnography data showed a median (IQR) central apnea-hypopnea index (AHI) of 4.1 (1.8-10.0) and obstructive AHI of 2.2 (0-8.0) events/h. We observed an inverse relationship between motor scores and central apnea-hypopnea indices. All children required ventilatory support at the end of the study period. Conclusion: This study showed abnormal polysomnography parameters and need for ventilation despite nusinersen suggesting ongoing need for regular monitoring with polysomnography. Understanding the respiratory disease trajectory of children

show abstract

Section: Discussionsupporting

confidence: 90%

Respiratory characteristics in children with spinal muscular atrophy type 1 receiving nusinersen

Xiao

Chiang

Castro‐Codesal

et al. 2022

Pediatric Pulmonology

View full text Add to dashboard Cite

show abstract

“…Traditionally, SMA and ALS are two distinct motoneuron diseases with progressive symptoms and severe disability. With the emergence of gene therapies, SMA patients achieve promising improvements in motor function and lifespan (Panagiotou et al., 2022; Waldrop et al., 2020). Moreover, early diagnosis and treatment are critical to therapeutic efficacy in SMA patients (Kong et al., 2021).…”

Section: Discussionmentioning

confidence: 99%

Comparison of neurofilament light and heavy chain in spinal muscular atrophy and amyotrophic lateral sclerosis: A pilot study

Dai

Sun

et al. 2023

Brain and Behavior

View full text Add to dashboard Cite

Background: Spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) were two major motor neuron diseases with similar symptoms and poor outcomes.This study aimed to identify potential biomarkers in disease monitoring and differential diagnosis of adult SMA patients with sporadic ALS patients. Methods:This was a pilot study with ten adult SMA patients and ten ALS patients consecutively enrolled during hospitalization. Serum and cerebrospinal fluid (CSF) samples were collected for assessment of neurofilament light (NFL) and phosphorylated neurofilament heavy chain (pNFH). Serum creatine kinase (CK) and creatinine (Cr) were also compared between groups. The receiver operating characteristic (ROC) curves were used to identify differentiated values among ALS and SMA patients.Results: Serum Cr, CSF NFL, and CSF pNFH levels of ALS patients were significantly higher than those of the adult SMA patients (p < .01). Serum CK and Cr were strongly correlated with baseline ALSFRS-R scores in SMA patients (p < .001). The ROC curves revealed an area under the curve (AUC) of 0.94 in serum Cr with a cut-off value of 44.5 µmol/L (Sensitivity 90%, Specificity 90%). AUC from the ROC curve of CSF NFL and CSF pNFH were 1.0 and 0.84, with cut-off values of 1275 pg/mL and 0.395 ng/mL, respectively (Sensitivity and Specificity of 100% and 100% in CSF NFL; Sensitivity and Specificity of 90% and 80% in CSF pNFH). Conclusion:CSF NFL and pNFH might be useful biomarkers for differential diagnosis of adult SMA and ALS.

show abstract

“…Several real-world studies followed, with somewhat conflicting results. In some, it was observed that respiratory function and time to invasive and non-invasive ventilation did not improve at the same pace as motor skills after nusinersen administration, although these outcomes were not monitored carefully (72)(73)(74)(75)(76)(77). In some studies on SMA type 1 patients, the need for respiratory support significantly increased over time (78)(79)(80)(81).…”

Section: Novel Sma Treatments and Their Impact On Sleep And Respirato...mentioning

confidence: 99%

Sleep and sleep-related breathing disorders in patients with spinal muscular atrophy: a changing perspective from novel treatments?

Abati,

Mauri,

Rimoldi

et al. 2024

Front. Neurol.

View full text Add to dashboard Cite

Spinal Muscular Atrophy (SMA) is an inherited neuromuscular disorder characterized by progressive muscle weakness and atrophy, resulting from the degeneration of motor neurons in the spinal cord. A critical aspect of SMA is its impact on respiratory function. As the disease progresses, respiratory muscles, in particular intercostal muscles, become increasingly affected, leading to breathing difficulties and respiratory failure. Without intervention, many children with SMA type 1 die from respiratory failure before their second year of life. While assisted ventilation has improved survival, it often results in ventilator dependence. The development of new SMN-augmenting therapies has renewed optimism, but their long-term impact on respiratory function is uncertain, and non-invasive respiratory support remains an important part of SMA management. Despite the importance of respiratory support in SMA, knowledge regarding sleep disorders in this population is limited. This review aims to synthesize existing literature on sleep and sleep-related breathing disorders in patients with SMA, with a focus on SMA type 1. We summarize evidence of sleep-disordered breathing and respiratory failure in SMA, as well as outcomes and survival benefits associated with non-invasive or invasive ventilation with or without pharmacological therapies. We also discuss current knowledge regarding the effects of novel disease-modifying therapies for SMA on respiratory function and sleep. In conclusion, optimal care for children with SMA requires a multidisciplinary approach that includes neurology and respiratory specialists. This review highlights the importance of monitoring sleep and respiratory function in SMA, as well as the potential benefits and challenges associated with assisted ventilation combined with new therapies.

show abstract

Changes in Ventilatory Support Requirements of Spinal Muscular Atrophy (SMA) Patients Post Gene-Based Therapies

Cited by 8 publications

References 64 publications

Respiratory characteristics in children with spinal muscular atrophy type 1 receiving nusinersen

Respiratory characteristics in children with spinal muscular atrophy type 1 receiving nusinersen

Comparison of neurofilament light and heavy chain in spinal muscular atrophy and amyotrophic lateral sclerosis: A pilot study

Sleep and sleep-related breathing disorders in patients with spinal muscular atrophy: a changing perspective from novel treatments?

Contact Info

Product

Resources

About