Evolution of bulbar function in spinal muscular atrophy type 1 treated with nusinersen

Weststrate, Harriet; Stimpson, Georgia; Thomas, L.; Scoto, Mariacristina; Johnson, Emily; Stewart, Alexandra M.; Muntoni, Francesco; Baranello, Giovanni; Conway, Eleanor; Manzur, A.; Munot, Pinki; Main, Marion; Au-Yeung, Claudia Kate

doi:10.1111/dmcn.15171

Cited by 24 publications

(30 citation statements)

References 32 publications

(81 reference statements)

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“…It is worth noting, however, that 14.6% of patients required GT due to an expectation of additional gains, especially concerning bulbar function. This data is in line with other published studies that have suggested that bulbar dysfunction has a less satisfactory response than the motor response in those patients treated with nusinersen [28,29]. At the end of follow-up in our study, the number of SMA type 1 patients on an oral diet increased from 15 (45.4%) to 18 (54.5%), an improvement also found in other real-life studies that used GT after prior use of nusinersen [30].…”

Section: Discussionsupporting

confidence: 93%

Real world safety and exploratory efficacy of gene therapy for patients with 5q-Spinal Muscular Atrophy in a Brazilian cohort

Mendonça

Ortega

Matsui

et al. 2023

Preprint

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Spinal muscular atrophy (SMA) is a motor neuron disease associated with progressive muscle weakness, ventilatory failure, and reduced survival. Onasemnogene abeparvoves is the first gene replacement therapy (GT) approved to treat this condition. An observational retrospective study was conducted to assess adverse events and efficacy of GT in SMA patients. Forty-one patients with SMA (24 females, 58.5% and 33 SMA type 1, 80.1%) were included. The mean age at GT dosing was 18 (± 6.4) months. Thirty-six patients (87.8%) were under previous treatment with nusinersen, and 10 (24.4%) continued nusinersen after GT. Mean CHOP-INTEND increased 13 points after 6 months and this finding did not differ between groups according to nusinersen maintenance after GT (p = 0.949). Among SMA type 1 patients, 14 (46.6%) reached the ability to sit alone. Liver transaminases elevation at least two times higher than the upper limit of normal value occurred in 29 (70.7%) patients. Thrombocytopenia occurred in 13 (31.7%) patients, and one presented thrombotic microangiopathy. Older age (> 2 years) was associated with more prolonged use of corticosteroids (p = 0.021). GT is effective in SMA patients, combined nusinersen after GT does not present additional gain in motor function, and older age is associated with prolonged corticosteroid use.

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Section: Discussionsupporting

confidence: 93%

Real world safety and exploratory efficacy of gene therapy for patients with 5q-Spinal Muscular Atrophy in a Brazilian cohort

Mendonça

Ortega

Matsui

et al. 2023

Preprint

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“…The FEES protocol described provides valuable information about the unique features. The few clinical tools already used in children with type 1 SMA [ 3 , 9 , 21 ] offer an initial basis, but in their current form, they are not suitable for future studies to make an adequate statement on swallowing status and development. Systematic test development and focus studies on this topic are urgently needed.…”

Section: Discussionmentioning

confidence: 99%

“…If left untreated, the children can never sit, mostly die within the first 2 years of life, or become dependent on supportive ventilation [ 8 ]. Due to the rapid death of motor neurons, complete loss of swallowing function is possible within a few weeks, requiring close monitoring of swallowing ability [ 1 , 2 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…Berti and colleagues conducted a retrospective analysis of possible clinical markers for oral abilities and feeding in an untreated cohort of 24 children [ 21 ]. Recently Weststrate et al [ 9 ] retrospectively assessed the bulbar function of 24 symptomatic children with type 1 SMA at the initiation of nusinersen and 6, 12, and 24 months after initiation. They used the six-point pediatric functional intake scale (p-FOIS) adapted from the original FOIS [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

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Flexible endoscopic evaluation of swallowing in children with type 1 spinal muscular atrophy

Zang

Johannsen

Denecke

et al. 2022

Eur Arch Otorhinolaryngol

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Purpose This study aimed to report on implementing flexible endoscopic evaluation of swallowing (FEES) in infants and toddlers with type 1 spinal muscular atrophy (SMA). In addition, a comparison of FEES results and clinical scores was carried out. Methods A prospective pilot study was conducted including ten symptomatic children with SMA type 1 (two SMN2 copies). They started treatment with one of the three currently approved therapies for SMA at a median age of 3.8 months (range 0.7–8.9). FEES was performed according to a standard protocol using Penetration–Aspiration Scale (PAS) and Murray Secretion Scale as a primary outcome. The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) for motor function, Neuromuscular Disease Swallowing Status Scale (NdSSS), Oral and Swallowing Abilities Tool (OrSAT), and single clinical swallowing-related parameters were also assessed. Results Distinct swallowing disorders were already evident in eight children at inclusion. The most common findings from FEES were pharyngeal secretion pooling, penetration, and aspiration of saliva and food as well as delayed initiation of swallowing. Despite an average increase in motor function, no comparable improvement was found in swallowing function. None of the surveyed clinical scores showed a significant dependence on PAS in a mixed linear model. Conclusions Valuable information regarding the status of dysphagia can be gathered endoscopically, particularly concerning secretion management and when oral intake is limited. Currently available clinical tools for children with type 1 may represent a change in nutritional status but are not yet mature enough to conclude swallowing ability. Further development is still required.

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“…The Penetration-Aspiration Scale (P-A score) was used for ratings of penetration and aspiration, and the Pediatric Functional Oral Intake Scale (P-FOIS) was used to measure current dietary intake. 3,8…”

Section: Methodsmentioning

confidence: 99%

Dysphagia and Lung Disease in Children With Spinal Muscular Atrophy Treated With Disease-Modifying Agents

et al. 2023

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Background/Objective:Disease modifying agents (DMAs) for treatment of Spinal Muscular Atrophy (SMA) has evolved the SMA phenotype with improved survival. Ongoing oropharyngeal dysphagia and respiratory complications are reported. The extent of dysphagia and respiratory morbidity in this population, since DMAs introduction, has not been well described.Study design and Methods:A whole population study involved all children with treated SMA type 1-3 in our facility. Videofluoroscopic swallow studies ([VFSS] type 1 only), Computer Tomographic chest (CT chest) scans, and clinical data were collected.Results:Thirty-six children were included (n=9 type 1, n=14 type 2, n=13 type 3; age range 0.3-15.4 years). Abnormal swallowing characteristics were demonstrated in all children with type 1 (n=8; 100%) . Bronchiectasis was found on CT chest: 3 of 9 (33.3%), 2 of 14 (14.3%), and 2 of 13 (15.4%) of type 1, 2, and 3 , respectively. Atelectasis, mucous plugging, bronchial wall thickening, and parenchymal changes were common.Discussion/ Conclusion:Swallow impairments were universal in children with type 1. Bronchiectasis was common in all paediatric SMA types, with a prevalence of 1 in 5. Routine monitoring and management of dysphagia/ recurrent respiratory infection should be implemented for improvement in lung health.

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Evolution of bulbar function in spinal muscular atrophy type 1 treated with nusinersen

Cited by 24 publications

References 32 publications

Real world safety and exploratory efficacy of gene therapy for patients with 5q-Spinal Muscular Atrophy in a Brazilian cohort

Real world safety and exploratory efficacy of gene therapy for patients with 5q-Spinal Muscular Atrophy in a Brazilian cohort

Flexible endoscopic evaluation of swallowing in children with type 1 spinal muscular atrophy

Dysphagia and Lung Disease in Children With Spinal Muscular Atrophy Treated With Disease-Modifying Agents

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