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

Abstract

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.

Consensus from the Brazilian Academy of Neurology for the diagnosis, genetic counseling, and use of disease-modifying therapies in 5q spinal muscular atrophy

“…Subsequent real-life studies with type 1 SMA patients, including those using the drug in an expanded access program, further confirmed the positive effects of nusinersen on motor and respiratory function, as well as on the survival of patients with long-term illness and varying respiratory conditions. 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 …”

“…Subsequent real-life studies with type 1 SMA patients, including those using the drug in an expanded access program, further confirmed the positive effects of nusinersen on motor and respiratory function, as well as on the survival of patients with long-term illness and varying respiratory conditions. [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] The CHERISH trial was a placebo-randomized study that enrolled 126 patients with late-onset SMA aged 2 to 12 years. 41 The study demonstrated that patients who received nusinersen experienced clinically significant improvements in motor function compared to the control group.…”

Longitudinal changes of swallowing safety and efficiency in infants with spinal muscular atrophy who received disease modifying therapies

“…These studies highlight the need for formal swallowing assessments, even after the administration of disease modifying therapies 14 . Notably, lung disease, secondary to aspiration, is one of the most detrimental comorbidities in patients with SMA, and it remains a concern in patients who receive disease‐modifying therapies, as demonstrated in a study that characterized the clinical and radiological findings of a cohort of patients with SMA, although this was performed in an older cohort of patients 12 . The above mentioned post hoc analysis demonstrated that, while all sixty five subjects had pulmonary stability at baseline, defined as the absence of aspiration or aspiration pneumonia, a few of them (five) did not meet this endpoint at the completion of the study period 14 …”

“…[5][6][7] Bulbar dysfunction is another recognized consequence of SMA, with resulting dysphagia and aspiration both in treated and untreated patients. [8][9][10][11] While safety and efficiency are important aspects of swallowing, available literature has primarily focused on safety [12][13][14] and less on efficiency. 15 Safe swallowing requires adequate airway protection from entry of ingested material through effective laryngeal vestibule closure, a tightly organized sequence of events required to protect the airway.…”

RegistrAME: the Spanish self-reported patient registry of spinal muscular atrophy

“…More than half of type 1 SMA patients with a gastrostomy were six years old or younger, because of their age, these patients were diagnosed when treatments were already available. This indicates the continued high impact of bulbar involvement in the posttreatment era [ 29 ] and the implementation of standards of care in the management of swallowing. Bulbar and respiratory function need to be closely monitored [ 30 ].…”