Our study found that quality of life of patients and caregivers differed across SMA types,disease-related and treatment characteristics. A significant difference among SMA types presented in the domain of neuromuscular diseases on the PedsQL NMM, with type III having the highest score and type I the lowest score. By contrast, Meaghann et al. found there was no significant difference among SMA types in the field of neuromuscular diseases in the proxy-report of the PedsQL NMM . A reasonable explanation for this finding is that in our study the sample size was larger than in the previous study and the children’s physical function was worse in severe types, indirectly reflecting the severity of the disease. Compared with patients with SMA types II and I, patients with type III had significantly higher scores in family resources, which is in accordance with the previous study . In contrast, our results showed there was no significant difference among SMA types in the communication domain. We infer that these negative results may be related to social and humanistic characteristics in China - that is, all patients received care and concern from their relatives, friends, community, and medical staff. This result further indicates that all members of Chinese society are concerned with children’s health. In terms of the total score of PedsQL NMM, patients with type III showed a significant difference compared with types II and I. These results are consistent with previous reports indicating that SMA types reflect the physical function of patients. Additionally, we also found the effect sizes were large or moderate in different subtypes of SMA, which indicated that the differences in quality of life of patients has reached the threshold of clinical relevance, which worth attention from health professionals. And we found there is no statistical difference in neuromuscular disease domain between children with type I and type II, but the effect size was moderate, which indicated that there was a clinical difference in neuromuscular disease domain between children with type I and with type II.
Our results showed that the physical, emotional, societal, and cognition items in the Family Impact Module were effective for comparing patients with different types of SMA. Patients with SMA type III tend to have higher scores than the other two types, which is related to the patients’ motor ability. The effect size SMA type III compared with type I and type II also indicated that there was a large clinical difference in the above functional domains. Most patients with SMA type III are able to walk alone, while patients with type II and type I cannot. However, because patients with type III can move their limbs freely and complete various functional exercises by themselves, their caregivers put less time and energy into their care, resulting in significantly higher family influence module scores in patients with type III than patients with types I and II. Our research showed that there was no significant difference among SMA types in communication, worry, daily activities, and family relations domains, which may be caused by the characteristics of China’s national social conditions, similar to the communication function outcomes seen in the PedsQL NMM.
Disease-related characteristics of patients with SMA such as skeletal malformation, digestive dysfunction, motor degeneration, and current motor ability obviously influence the PedsQL NMM and PedsQL FIM results. SMA is a disease often involving dysfunction of multiple systems, as seen in the reduction in the distribution of SMN protein to the body’s multiple organs and tissues [10, 11]. As SMA is a progressive disease, some complications such as skeletal malformation, digestive disorders, respiratory disorders, and motor function degeneration appear gradually. Our findings showed that the total score, neuromuscular disease score, and family score of PedsQL NMM were significantly lower in patients with these complications than in those without them. Our results support the findings from previous study - that is, motor function is reduced in patients with skeletal deformities, which in turn affects all aspects of the patient’s life . Digestive disorders make malnutrition a higher risk in patients, which may cause fatal or serious disorders [27, 28]. The degeneration in motor ability and current movement ability can indirectly reflect the patient’s survival condition, and all of the disease-related characteristics can have a significant effect on QoL. In the PedsQL FIM, the physical and emotional functions of the caregivers of patients with skeletal malformations were worse than those of the caregivers of patients without skeletal malformations. The skeletal malformations of patients with SMA often include scoliosis, muscle contracture, dislocation of hip joint, and other conditions, which often lead to the degeneration or loss of motor ability . Faced with this situation, caregivers have to increase the daily nursing level of patients to achieve a high QoL. For so long caregivers’ physical health and mental health are greatly affected. Dysphagia and other digestive disorders often appear in the last stage of SMA, which seriously affects the patients’ physical health, and reduces their caregivers’ QoL and family relationships. Individual physical and psychological functions may be significantly affected by mobility, and the caregivers of patients who can walk freely require less care and energy than the caregivers of patients who have lost the motor ability to walk. This means that when caregivers concentrate their energy on their children, the caregivers have frequent and serious limits to their own lives and increased stress on their own bodies, which in turn can lead to the onset of anxiety, fear, depression, and other physical or mental side-effects. In addition to the statistical significance, effect sizes in terms of the above-mentioned domains were moderate or large, which indicated disease-related characteristics may impact quality of life of patients and caregivers, which warranted attention from clinical professionals during their practice.
Our results suggest that clinical treatments improve QoL in patients with SMA from the caregivers’ perception. Early exercise training is beneficial to improving the recovery of limb function, and muscle-strengthening activities help patients regain strength and stability [30, 31]. Various studies indicate that exercise training at the recovery stage can effectively lower the disability level of stroke patients with hemiplegia and improve their QoL [32–34]. They also suggest that exercise training can activate the motor neurons of the body to promote the recovery of and effectively improve the motor function of patients with neuromuscular degeneration disease, including Duchenne muscular dystrophy and SMA . Studies have demonstrated that exercise training is safe and feasible, prolongs survival, diminishes muscle weakness, and enhances motor behavior . While not statistically significant, we observed a strong trend for exercise training to greatly increase the neuromuscular disease and family resources scores. However, the effect size reflects that whether exercise training is carried out or not has a moderate difference in clinical works. This trend suggests that exercise training is helpful in the recovery of motor function in patients with SMA and may delay the degradation of motor function, which can effectively improve the QoL of patients.
Numerous studies have shown that the most common causes of death in patients with SMA involve respiratory complications [36, 37]. As the disease progresses, patients may experience changes in their organ systems, especially the respiratory dysfunction, which occurs later. Without respiratory support, most patients with SMA type I die of pneumonia and respiratory failure before the age of 2 years . However, our study suggests that patients with respiratory support have lower neuromuscular disease and family resources scores compared with those without respiratory support. One possible explanation for this unexpected result is that patients receive respiratory support when their condition has deteriorated, which in turn seriously affects their QoL and simultaneously requires caregivers to spend more energy in managing daily life. Many studies have confirmed that respiratory support is helpful in improving pulmonary function as SMA is a progressive disease involving multiple system dysfunction, including respiratory complications, and patients with type I often die of respiratory failure. Based on our findings, we suggest that patients with SMA type I should adopt mechanical ventilation strategies early to maintain respiratory function effectively, preventing respiratory complications and pulmonary infections, and subsequently improving their QoL.
Recently, nusinersen became the first effective drug treatment for SMA available in China. As previous research noted, nusinersen treatment can improve the motor, respiratory, digestive, and other system functions in patients [39–42]. In our study, six caregivers of patients who were receiving nusinersen treatment complete the PedsQL NMM. Although the questionnaire results for these six patients showed that the neuromuscular diseases and family resource scores were higher than those of patients who did not use nusinersen, the caregivers of these six patients reported that drug treatment effectively improved the patients’ QoL. We cannot make definite conclusions on whether their QoL was improved by nusinersen use because of the small sample size. These patients also received exercise training, so it is possible that a combination of the two factors increased QoL. The sample size should be increased in follow-up studies and should include an extended course of nusinersen treatment to verify whether this treatment improves patients’ QoL.
Health management has been defined as an integrated approach to assess, guide, and intervene in the risk factors affecting the health of a group or an individual, based on the modern concept of health and the new medical models and with the theories, techniques, and means of modern medicine and management . Multidisciplinary management is composed of more than two related disciplines in order to implement clinical treatments for specific diseases [44, 45]. The results of this study showed that the total score of the PedsQL NMM for patients receiving multidisciplinary management intervention was superior to that of the non-MDT management group (p < 0.05), indicating that MDT management can effectively improve the QoL of patients with SMA. And the effect size between non-MDT management group and MDT group are moderate, combined the statistical difference were more confirmed reflects the significant clinical benefits of participation in the MDT group. As shown in previous studies of MDT management in other chronic diseases, such as tuberous sclerosis complex (TSC), Prader-Willi syndrome, pediatric chronic pancreatitis, pediatric medulloblastoma, and asthma, this approach is conducive to ensuring the best outcomes of disease, improving patients’ daily life, reducing caregiver burden, and decreasing healthcare load [46–49]. Low awareness of MDT health management interventions among caregivers often results in ignoring other system dysfunction symptoms, which may lead to delayed treatment of SMA. Based on our observations and previous studies, we suggest that raising the caregivers’ awareness of MDT health management, monitoring the status of system dysfunction, guiding patients treated with related systems concerning the progress of disease, and improving the patients’ QoL can substantially improve the lives of patients and their caregivers.
The highlights of this study are that it is the first to evaluate and investigate the QoL of Chinese patients with SMA and to reflect the QoL of the children according to the perceptions of the caregivers. Moreover, this study analyzed the disease-related characteristics of the patients and the influence of clinical treatments on the QoL and the family impact. Previous studies have not provided data on the QoL of patients with SMA in China, and there are few studies on the influence of clinical treatments on QoL in SMA. Considering the social, economic, and medical characteristics in China, which are different from other developed countries, the QoL survey of patients with SMA in China has become an interesting and emerging research field.
Our study had several limitations. First, the sample size included in this study is modest, reflecting the rarity of the disease, and the statistical effectiveness of our analysis is limited as well. A second limitation of this study is that patients were only sampled from central and east China. Given the lack of QoL survey data on patients with SMA in other regions, the study may not be representative of the QoL of patients with SMA across China. Nevertheless, our results may be generalized to patients from the areas mentioned above. Third, this study was a cross-sectional cohort study with data collected at a single time point, which precluded drawing conclusions regarding causality. Further, the study reflected the influence of disease-related characteristics on the QoL of children and the initial effect of medical measures only. Finally, although the PedsQL is designed to be used for all types of disease, it has not been specifically validated for proxy-reported use in children with SMA.
To sum up, further longitudinal follow-up of these patients should be conducted and QoL indicators should be used to investigate the effectiveness of clinical treatments for childhood SMA. Furthermore, future studies need larger sample sizes and should pursue multicenter enrollment to involve patients with SMA from all of China to obtain a database that reflects the QoL of patients across the country. In addition, with the continuous progress in the diagnosis and treatment of SMA, larger patient sample sizes, especially in the drug treatment group, should be included in subsequent studies to confirm the effectiveness of treatment approaches and to make the results more generalizable.