Our study found that quality of life of patients and caregivers differed across SMA subtype, disease-related characteristics, and treatment characteristics. We found a significant difference among SMA subtypes in the PedsQL NMM domain of Neuromuscular diseases, with type III having the highest average score and type I having the lowest average score. By contrast, Meaghann et al. found no significant difference among SMA subtypes in the domain 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 of SMA types II and I, patients of type III had significantly higher average scores in the Family resources domain, which is consistent with the previous study . In contrast, our results revealed no significant difference among SMA subtypes in the Communication domain. 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 also suggests that all members of Chinese society are concerned with children’s health . In terms of the average 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, which indicate that SMA subtypes reflect the physical function of patients . Additionally, we also found that effect sizes were large or moderate in different subtypes of SMA, which indicated that the differences in quality of life of patients had reached the threshold of clinical relevance and was worthy of attention from health professionals. We found no significant difference in the Neuromuscular disease domain between children with type I and type II; however, but the effect size was moderate and indicated a clinical trend with the QoL of type II being higher than that of type I in the Neuromuscular disease domain. These results suggest that more attention to this trend should be paid to improve the QoL of SMA patients.
Our results showed that the physical, emotional, societal, and cognition functioning domains of the Family Impact Module were effective for comparing patients with different subtypes of SMA. Type III patients tended to have higher scores than the other two subtypes, which is related to the patients’ motor ability because most type III patients have the ability to move autonomously and the large scope of activities can improve their physical and mental health. The effect size SMA type III compared with type I and type II also indicated a large clinical difference in the above functional domains. Most patients with SMA type III are able to walk alone, whereas patients with type II and type I cannot. Because patients with type III can move their limbs freely and can 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 type III patients than in patients with types I or II. Our research showed no significant difference among SMA types in the Communication, Worry, Daily activities, or Family relations domains. This result may have been caused by the characteristics of China’s national social conditions, similar to the Communication domain 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, complications such as skeletal malformation, digestive disorders, respiratory disorders, and motor function degeneration appear gradually. Our findings showed that the average Total score and the average scores of domains Neuromuscular diseases and Family resources of PedsQL NMM were significantly lower in patients with these complications than in those without them. Our results support the findings from a 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 [28, 29]. The degeneration in motor ability and current movement ability can indirectly reflect the patient’s survival condition, and all of these 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 disease status of skeletal malformation in SMA patients with progressive muscular atrophy and muscle weakness is a cumulative effect of a causal chain. 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 . In the meantime, severe progressive muscle weakness and muscle atrophy lead to skeletal malformations in SMA patients, which can further worsen the regression of motor ability in SMA patients. In this way, a kind of progressive circulation and accumulated effect is formed between skeletal malformations and the degeneration or loss of motor ability [13,14,30]. 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 patient’s physical health and reduces the caregiver’s 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 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 placed on their own lives and have increased stress on their own bodies. These detrimental effects can lead to the onset of anxiety, fear, depression, and other physical or mental side-effects . In addition to the statistical significance, the effect sizes in that we estimated for the above-mentioned domains were moderate or large, indicating that disease-related characteristics may impact the QoL of patients and caregivers, which warrant attention from clinical professionals during their practice.
Our results suggest that clinical treatments improve QoL of patients with SMA from the caregivers’ perception. Early exercise training is beneficial for improving the recovery of limb function, and muscle-strengthening activities help patients regain strength and stability [32, 33]. Various studies indicate that exercise training at the recovery stage can effectively lower the disability level of stroke patients with hemiplegia and can improve their QoL [34-36]. These studies also suggest that exercise training can activate the motor neurons of the body to promote the recovery of and to 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 increase average scores in the domains Neuromuscular disease and Family resources. However, the effect sizes reflected that whether exercise training was carried out or not had a moderate difference. This trend suggests that exercise training may be 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.
Several studies have shown that the most common causes of death in patients with SMA involve respiratory complications [38, 39]. 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 had lower average scores in the domains Neuromuscular disease and Family resources compared to patients 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 because SMA is a progressive disease involving multiple system dysfunction, including respiratory complications. Patients with type I often die of respiratory failure. Based on our findings, we suggest that patients with SMA type I adopt mechanical ventilation strategies early to maintain effective respiratory function, preventing respiratory complications and pulmonary infections, and subsequently improving QoL.
Recently, Nusinersen became the first effective drug treatment for SMA available in China. As noted in previous research, Nusinersen treatment can improve the motor, respiratory, digestive, and other system functions in patients [41-44]. In our study, six caregivers of patients who were receiving Nusinersen treatment and also receiving SOC completed the PedsQL NMM. Although the questionnaire results for these six patients showed that the average scores of domains Neuromuscular diseases and Family resources were higher than those of patients who did not accept Nusinersen treatment, the caregivers of these six patients reported that drug treatment effectively improved the patients’ QoL. We cannot make definitive conclusions on whether their QoL was improved by Nusinersen treatment owing to 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 if 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, new medical models, and the theories, techniques, and means of modern medicine and management . Multidisciplinary team (MDT) management is composed of more than two related disciplines in order to implement clinical treatments for specific diseases [46, 47]. The results of this study showed that the average Total score of the PedsQL NMM for patients receiving MDT 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. The effect size between non-MDT management group and MDT group was moderate, but still indicates 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, to improving patients’ daily life, to reducing caregiver burden, and to decreasing healthcare load [48-51]. 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 [13,14].
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 these 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 few studies exist on the influence of clinical treatments on QoL in SMA. Considering the social, economic, and medical characteristics in China, which are different from those of other developed countries, the QoL survey of patients with SMA in China has become an interesting and emerging research field.
Except for the Communication module, our survey was given a lower mark than those of previous studies conducted in foreign populations. The present situation can be explained by the following reasons: First, China is a developing country while American/European countries are developed ones. The cost of treatment is prohibitive for most SMA patients in China, and they cannot receive the early diagnosis and treatments obtained by patients of foreign countries. Second, the development of diagnosis and treatment of SMA in China is slower than that in foreign countries, drugs on the market later than foreign countries. Third, the United States has incorporated SMA into newborn screening and has attached great importance to the diagnosis and treatment of SMA; whereas China is still in early stages. However, the average score of the Communication domain in our research was higher than that of foreign studies.
Our study had several limitations. First, the sample size included in this study is modest, reflecting the rarity of the disease. We have not applied self-report in our study because the sample size would be even smaller if we only included children older than five years. In the future study, we recommended more larger samples could apply both self-reported and proxy-reported QOL measurements among patients with SMA to get a full picture of patient’s QOL. A second limitation of this study is that patients were only sampled from central and east China. Given the lack of QoL surveys on SMA patients in other regions, the study may not be representative of the QoL of SMA patients across China. Nevertheless, our results may be generalized to patients from the areas mentioned above. Third, this study was a cross-sectional study with data collected at a single time point, which precluded drawing conclusions regarding causality. Fourth, owing to less data of specific items of clinical treatments, our study cannot provide a more in-depth analysis; so future research is needed with a larger sample that includes subsets of clinical treatments. In addition, our study reflected the influence of disease-related characteristics on the QoL of children and only the initial effect of medical measures. Finally, although the PedsQL is designed to be used for all types of neuromuscular diseases, this survey instrument has not been specifically validated for proxy-reported use in children with SMA in China.
In summary, further follow-ups of these patients should be conducted and QoL indicators should be used to investigate the effectiveness of clinical treatments for childhood SMA. In addition, future studies need larger sample sizes and should pursue multicenter enrollments to involve patients with SMA from all of China to generate a database that reflects the QoL of patients across the country. To confirm the effectiveness of treatment approaches and to make the results more generalizable, subsequent studies should continue research in the diagnosis and treatment of SMA, and should include larger numbers of patients, especially in the drug treatment group.