Oral and Swallowing Abilities Tool (OrSAT) for Type 1 SMA Patients: Development of a New Module

LIST OF ABBREVIATIONS

INTRODUCTION

Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by mutations in the SMN1 gene, leading to motor neuron loss and subsequent muscular atrophy and weakness. Type 1 is the most severe form of SMA, characterized by severe hypotonia, weakness and increasing respiratory, swallowing and feeding difficulties over time [1]. As type 1 includes patients with different degree of severity, it has been proposed that it could be subdivided into three main subgroups: 1.1, the more severe end of the spectrum with early, severely reduced mobility, respiratory and bulbar difficulties; 1.5, the most common phenotype, with inability to raise the legs against gravity or to maintain the head posture but no overt feeding or respiratory difficulties at diagnosis; 1.9, the mildest phenotypes, infants may achieve head control [2, 3]. The three subgroups grossly overlap with the subtypes 1 A, B and C, proposed in another classification more based on age of onset [3, 4].

Improvements in standards of care [5, 6] and the advent of new therapeutic approaches have resulted in a dramatic improvement in survival and functional abilities in these patients, changing the course of the disease [7–10]. So far, most of the attention has been focused on survival and motor or respiratory outcome [11]. Despite feeding being one of the most important aspects in the care of type 1 SMA, less has been reported about possible changes in oral and swallowing abilities in the treated patients. This is at least partly due to the paucity of available specific tools to assess these aspects, especially in the first years. While there are a number of outcome measures designed to assess motor function, such as the CHOP INTEND [12] or scales assessing motor developmental milestones [13, 14] there are no dedicated tools for the assessment of swallowing and oral motor skills in type 1 SMA or in general, in weak young infants in the first 24 months of life. One of the challenges in this age group, especially in the first year after birth, is that the level of abilities increases with age, with changes in feeding modalities and in the consistency of food texture [15]. Also, the volume of food needs to increase as the child grows to provide adequate nutrition to support growth. As such, even in the absence of overt dysphagia there may be an element of oral-motor fatigue that precludes adequate caloric and fluid intake. In the handful of studies reporting feeding related issues in SMA patients, with few exceptions, do not include or only include few type 1 infants [16–20]. A very recent study used an observation list and recorded different parameters during a feeding session [21]. In another study nutritional aspects were assessed as part of a survey [22].

The Neuromuscular disease swallowing status scale (NdSSS) has recently been used in a large neuromuscular cohort including 11 type 1 infants [23]. The NdSSS is an 8-stage scale, designed to evaluate swallowing conditions that are frequently encountered in progressive neuromuscular disorders in various clinical settings, that can be used by nonprofessionals without special knowledge [24]. However, it was not specifically designed for infants and does not capture some aspects such as fatigue during the nursing sessions or need of specific positioning during meals, that are relevant for type 1 patients.

In this paper we describe the development of a new tool specifically designed to record different aspects related to oral and swallowing abilities in type 1 SMA patients that can be easily used in a clinical setting, in infants from the first months after birth until 24 months of age. We also report the application of the new tool to a cohort of typically developing infants of the same age and to a cohort of type 1 SMA patients.

MATERIALS AND METHODS

The aim of our effort was to develop a tool that could be easily used in the clinical routine, not requiring expensive instruments or invasive diagnostic procedures, but still able to capture a number of aspects related to oral abilities and swallowing, recorded using a structured format. As some of these aspects are likely to change over time with increasing age or for other reasons, such as disease progression or possible intervention, we stratified the items according to age and added an easy scoring system in an attempt to quantify the possible changes in the individual items at different ages. The new tool includes a checklist assessing individual aspects of swallowing or related to the use of orofacial muscles. A separate section summarizes the functional abilities into levels of impairment.

The checklist was based on our clinical experience, including the questions that are routinely asked in our clinical setting by clinicians at each visit as part of the clinical history, but adding a more structured format and a scoring system.

The second part reporting a description of levels of impairment was based on clinical experience and review of the literature.

The development of the tool followed a number of steps:

RESULTS

The OrSAT was used in 24 type 1 patients who had been attending our Clinic in the last few years in whom the same information collected by the new tool had been previously recorded using a less-structured format.

The scores on the checklist ranged between 0 and 7 in the assessments performed before 6 months (mean: 3.43, SD: 2.15), between 0 and 10 in those performed between 6 and 10 months (mean: 3.16, SD: 3.64), and between 0 and 12 in those older than 10 months (mean: 5.39, SD: 4.38) (Fig. 1).

Fig. 1

Individual details of the scores in the different subgroups according to severity highlighted by age range (0–5; 6–9; 10–24 months). The shaded areas corresponds to the maximum total score of the tool corresponding to what is expected in neurotypical infants.

1.9

Type 1.9 infants were generally assessed after 6 months. At 9 months the CHOP INTEND scores ranged between 28 and 41. None of the infants required tube feeding. The OrSAT checklist total score was more than 9 in 3/8, 8 in 4/8 and 5 in one infant.

Fig. 2

Change in levels of impairment in the study cohort subdivided by SMA 1 decimal classification and visits: Each symbol corresponds to a single patient at each given age (open dot ○: no impairment; barred dot ø: mild impairment; grey dot •: moderate impairment; full dot •: severe impairment; the symbol –was used when an evaluation was not performed).

At one year of age, the CHOP INTEND scores ranged between 25 and 39. The OrSAT scores showed minimal changes, with only a few infants requiring intervention, tiring during the nursing session and showing a longer duration. Tiredness during the nursing session and duration of the meal were also the items most frequently impaired from 12 months onwards. At 24 months the total score at the CHOP INTEND ranged between 20 and 35, and the total score at the OrSAT was more than 9 in 4/8, 8 in 2/8, 2 in one and 1 in another one infant. None of the 1.9 infants had weight below 2SD or required tube feeding with exception of one at the age of 18 months.

The difference between 1.1, 1.5 and 1.9 was significant both at baseline (p < 0,001) and when the follow up changes were considered (p = 0,001).

1.9

Before the age of 9 months all the patients who had been diagnosed and could be assessed had no impairment. At 9 months 7 of the 8 had no impairment and 1 had mild impairment. Moderate or severe involvement occurred only in 2 patients by 18 months.

7. Correlation between functional levels and checklist scores

In infants below the age of 6 months, in whom the possible maximum score on the checklist is 7, all infants labeled as with no impairment on the classification of level impairment had scores of 6 and 7 on the checklist. Those labeled as with mild impairment had scores of 4 and 5, those with moderate impairment had scores of 2 and 3 and those with severe impairment all had a score of 0. The correlation coefficient was 0.984.

In infants between 6 and 9.99 months, in whom the possible maximum score on the checklist is 10, all infants labeled as with no impairment had checklist scores between 7 and 10, those with mild impairment had scores of 5, those with moderate impairment had scores of 3 and those with severe impairment all had as a score of 0. The correlation coefficient was 0.951.

In infants > 10 months, in whom the possible maximum score on the checklist is 12, all infants labeled as with no impairment had scores between 9 and 12, those with mild impairment had scores between 5 and 8, those with moderate impairment had scores between 3 and 4 and those with severe impairment all had as a score of 0 (Fig. 3). The correlation coefficient was 0.983.

Fig. 3

Correlation between total OrSAT checklist scores and age in different subgroups subdivided according to the OrSAT level of impairment. (○: no impairment; barred dot ø: mild impairment; grey dot \color grey•: moderate impairment; full dot •: severe impairment. Each symbol corresponds to a single patient. The shaded areas identify the maximum total OrSAT checklist score expected in typically developing infants at different ages (grey 0–5 months; Pink 6–9 months green: 10–24 months).

DISCUSSION

Dysphagia is one of the most critical aspects of care of type 1 SMA patients, who often present weakness affecting the various phases of feeding abilities, that may involve not only the pharyngeal phase (decreased airway protection in combination with weak swallowing) but also sucking and handling of oral secretion [19]. Both the first version and the revised care recommendations [5, 6, 28] highlight the importance of regular speech therapist assessments to monitor these aspects, suggesting to observe feedings and a careful evaluation of possible difficulties related to feeding [5, 6]. For non-sitters, a swallow study is recommended shortly after diagnosis and, if the initial test is normal, closely monitored to detect possible early signs of feeding difficulties.

An effort has been made, at least in tertiary care centers, to implement regular clinical and radiological assessments in clinical practice, as they were not always routinely available for the lack of specialized speech and language therapists, physicians, and radiologists with interest and expertise in this field. As type 1 infants have very frequent visits to the centers for the administration of the new therapies and other assessments, there has been an increasing need to regularly collect structured information by mean of an easy clinical tool that could be easily updated at each appointment and used as a complement to the full speech therapist assessments performed at fixed intervals.

Despite the clinical relevance of dysphagia in type 1 infants, it is surprising how little effort there has been to develop disease specific tools aimed to identify different aspects of oral motor or swallowing difficulties. Even in the recent trials, swallowing was not formally investigated with a structured assessment and was often defined by the need for tube feeding [7, 29]. Only in the gene replacement trial the request to report the ability to swallow thin liquids was used [8].

We report the development of a new tool providing a simple assessment of oral abilities and swallowing in type 1 infants by using a checklist aimed to systematically record aspects of oral motor and swallowing function that are often assessed in clinical routine but not in a structured format. The checklist also provides the possibility to quantify the severity of impairment by using a very simple scoring system.

While this checklist is not meant to replace the more structured observer rated speech therapist assessment internationally recommended, it provides a measure of the parents’ perception of their child’s swallowing ability that also covers possible episodes occurring at home that may not be seen during a single observation in clinic. The use of patient reported measures has been strongly encouraged both by regulatory authorities both in Europe (‘Reflection Paper on the Regulatory Guidance for the use of Health Related Quality of Life (HRQL) Measures in the Evaluation of Medicinal Products’) and US (Guidance for Industry. Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims. US DHHS, FDA) as these tools can provide better understanding of the impact caused by disease and treatment on the patient.

Our checklist was developed using a template of questions that were routinely asked in our clinical setting, adding two items assessing the oral motor aspects of language. While language was in the past rarely observed in type 1 infants, following the advent of the new therapies there is an increasing number of patients in whom is possible to monitor language development over the first years. One of the challenges with developing an assessment for infants as young as newborns as well as infants in the first years after birth is that it should take into account age related changes, especially at the time when infants switch from a fully liquid diet to the introduction of new textures. Because of this, we defined age specific items and maximum possible scores for different ages.

We also designed a separate classification reporting functional levels, as a complement to the checklist, based on other tools used in other disorders and in a wider age range, simplified for the exclusive use in young infants in a clinical setting.

In order to explore the ability of the checklist and of the functional levels to detect possible changes over time in type 1, we retrospectively applied these tools to a cohort of type 1 infants longitudinally followed in our Unit. The results show a clear separation in swallowing abilities among infants with different severity of SMA, both at baseline and at follow up (p < 0.01). Infants with the most severe form, nearly invariably had some swallowing difficulties. Their follow up showed that already by six months, in all the survivors there was the indication for tube feeding. All but one had a score of zero at all time points and only at three months very few infants were able to swallow liquids even though they tired very easily and required compensatory postures and liquid thickening. Even in those with relatively better scores there was already an indication for introducing tube feeding.

At the other end of the spectrum, infants with type 1.9 not only had high scores at the time of diagnosis, that was often after 3 months, but had an increase in their total scores with increasing age, often reaching the ceiling of the age appropriate maximum scores. Interestingly, despite the good scores, some of these infants were still reported to be tired and had an increased duration of the nursing session time. There was also some ‘delay’ in the time when solid food was introduced as reflected by the changes in the scores related to this activity. Patients with the ‘intermediate’ type 1 phenotype, 1.5, had a more variable progression and most of them reached a score of 0 between 6 and 12 months. It is of note that in the first 6 months in most patients their carers did not report problems with swallowing liquids, choking episodes or other concern, but often reported that the children tired easily during feeding and they often needed short and frequent meals. Tiredness and need for intervention often preceded more obvious difficulties requiring more structured intervention after the age of 6 months. These findings were quite consistent even in the milder type 1, clearly indicating that they should be regularly assessed and discussed with families and other operators involved in the care of the patients.

The subdivision of our cohort into clinical subtypes allowed a more precise definition of the trajectories and to reduce the variability reported in previous studies. A recent study, using the Neuromuscular Disease Swallowing Status Scale (NDSSS) and Videofluoroscopy swallowing studies in type 1 infants in the first 2 years, reported that on average swallowing function deteriorated at 6 months with a large variability of the time when tube feeding was needed [23]. A previous survey in type 1 patients with a wider age range also reported similar variability but with an average age of feeding tube placement of 11 months [22].

Not surprisingly, the checklist scores were associated with the functional levels that were independently recorded capturing other aspects, such as posturing or use of alternative ways of feeding that are not captured in the checklist. By using the two tools together, we were able to establish which checklist total scores were associated with each level in the different age groups.

These results should be interpreted with caution as these findings are strongly limited by the retrospective use of the tool. While we would have ideally started a new data collection to prospectively establish the possible changes and natural history of swallowing abilities, at the time we developed the final version, all our type I patients were on treatment with Nusinersen or in clinical trials. The only chance to observe possible changes in untreated patients was therefore to use the recent retrospective data. The use of both the not structured format used in clinical practice in the past and the structured OrSAT checklist in a small sample of prospectively enrolled patients showed a good concordance. This suggests that, even if with caution, these results may provide at least an indication of the ability of the new tool to capture changes over time in type 1 infants and some reference data in untreated type 1 patients.

Our findings indicate that, in addition to the items assessing choking and possible unsafe swallowing, particular attention should be paid to those assessing fatigue during the nursing session, as this was the most frequent finding even in infants who did not have any other obvious sign of swallowing difficulties. These results are in agreement with a recent study using a more structured observer rated approach who also showed that shortened nursing sessions were extremely frequent [19]. These aspects should therefore be systematically explored with specific questions as parents often increase the frequency of feeding to compensate the short duration of nursing sessions, underestimating the importance of these findings.

Further work is needed to complete the validation of the new tool and to fully explore its possible use in clinical and research settings. In our study the checklist was always performed by a clinical examiner interviewing the carers and further work is required to establish the reliability of the tool as a self-administered patient reported measure.

Further studies exploring the new tool, also in relation to the more structured and complete assessments performed by speech therapists, will provide additional information on the sensitivity of this new tool as a clinical routine screening tool. Our preliminary results suggest that our structured examination reporting parents’ perception could be potentially used at each clinical appointment to provide some general information, especially when time and resources for more structured assessments are limited. Further work is also requested to further explore the ability to talk that is becoming increasingly achieved in treated patients. This will become particularly important at the time the scale will be used in infants treated with the new available therapies.