Impact of regular physiotherapy intervention on the function and quality of life of pediatric patients diagnosed with Mucopolysaccharidosis

Abstract

Objectives

We aimed to determine the impact of regular physiotherapy (PT) intervention, tailored to the individual needs and physical limitations of children with Mucopolysaccharidosis (MPS), on their function and quality of life (QoL).

Design

Prospective longitudinal mixed methods study

Participants

Eligible patients diagnosed with MPS followed in the Lysosomal Disease Clinic at our center.

Intervention

Patients were seen for five regular physiotherapy visits over 12 months. Our clinic's physiotherapist designed a physiotherapy assessment form and created individualized home exercise programs (HEPs) for MPS patients.

Outcome measures

Health-related quality of life was measured using the Pediatric Quality of Life Inventory™ (PedsQL). A descriptive analysis approach was used to identify trends in PedsQL survey data and physiotherapy outcomes

Results

15 participants were enrolled; however, only 7 completed the entire study. Participants who completed at least two study visits demonstrated improved PedsQL™ scores between the first and last visits, except for one participant. The majority of participants who completed the entire study presented with stable or improved findings for function, strength, balance, range of motion, and pain

Conclusion

We found that physiotherapy intervention is a safe adjunct to existing therapies and might allow children to maintain their functional status, decrease pain, and improve quality of life.

Highlights

• •PT is safe and likely beneficial for all children diagnosed with MPS, regardless of subtype
• •Physiotherapists can help manage symptoms to maximize QoL for children diagnosed with MPS
• •PT might allow children diagnosed with MPS to maintain their functional status and decrease pain
• •This study demonstrates the importance of tailoring specific PT interventions for patients diagnosed with rare diseases to promote their QoL

1. Introduction

Mucopolysaccharidoses (MPSs) are a group of rare metabolic genetic conditions characterized by an accumulation of glycosaminoglycans (GAGs). This accumulation is a result of deficiencies in lysosomal enzymes [1], [2], [3]. The build-up of GAGs leads to tissue damage and multi-system dysfunction [1], [2], [3]. Clinically, individuals affected by MPSs can present with central nervous system involvement, compromised respiratory function, cardiac disease, and skeletal abnormalities [1]. There are seven types of MPS syndromes, all of which have symptoms that progressively worsen over time [1], [4]. The literature on MPS suggests that early diagnosis and therapeutic intervention are critical [1], [3]. There is currently no cure for MPS; however, treatments available include Hemopoietic Stem Cell Therapy (HSCT) and Enzyme Replacement Therapy (ERT) [1]. These therapies have been shown to improve and or stabilize some of the clinical features of MPS and thus enhance the overall prognosis of the disease. However, joint contractures, stiffness, and pain may persist, which could have a considerable effect on an individual's function [1], [2]. Physical function and pain are especially important when considering factors related to a patient's quality of life (QoL), as independence with mobility allows children to explore their environment and attain motor milestones [2]. Therefore, a non-invasive and non-pharmacological alternative such as physiotherapy (PT) intervention may help to address musculoskeletal features and offer benefits in preserving joint function, reducing pain, maintaining mobility, and improving QoL.

Several studies have been published to outline the physical manifestations of MPS and the potential benefit of involving physiotherapy services to improve an individual's function. Dusing, Thorpe, Rosenberg et al. examined the gross motor abilities of four children with Hurler Syndrome (MPS I) [2]. This case study found that all participants presented with gross motor delays and limitations in range of motion (ROM) [2]. These researchers believe that children with Hurler syndrome should be referred to PT services to improve their gross motor skills, strength, and ROM [2]. This is supported by the research conducted by Wood, Cleary, Alderson et al., which investigated the effects of Hunter syndrome (MPS II) on gait [5]. They found that participants had asymmetrical and decreased step lengths compared to a typical gait pattern, likely due to decreased ROM affecting the swing phase of gait [5]. They also reported that tight musculature could affect heel strike and the individual's base of support [5]. Furthermore, a different group of researchers described the impact of Morquio A Syndrome (MPS IVA) on the musculoskeletal system and outlined that PT intervention might be beneficial for all patients to maintain physical function [4]. This was also acknowledged by Akyol, Alden, Amartino et al., who recommended that regular assessments by physical therapists should be conducted in adult and pediatric patients with MPS IVA to assess limb function [3]. In addition, they suggested that PT interventions may improve QoL by enhancing functional abilities [3].

These authors all agree that the progressive nature of MPS significantly impacts the QoL and functional abilities of individuals impacted by this condition [[2], [3], [4], [5]], but there is currently a paucity in research that documents the longitudinal outcomes of regular physiotherapy intervention for children with MPS. Therefore, the purpose of this study was to assess the effect of PT intervention with repeated assessments and prescription of individualized home exercise programs (HEPs) on QoL, pain, and function over time for children with MPS.

2. Methods

This was a prospective longitudinal, single-center, single-arm, mixed-methods study conducted at our medical center. The methodology included both qualitative (patient experience and pain reporting) and quantitative (ROM measurements, strength measurements, and QoL survey) data.

2.1. Participant eligibility

The study sample was composed of patients actively followed in the Lysosomal Disease Clinic (LSD) at our institution. Individuals were eligible if they were between 2 and 18 years of age, with MPS diagnosis confirmed either molecularly or biochemically through reduced enzyme activity. For safety reasons, those with contraindications to PT intervention before or after initial assessment were excluded from the study. For example, those with musculoskeletal instability, cardiorespiratory contraindications, or hemodynamic instability. For patients who presented with relative precautions, such as neurological risks or orthopedic-related pain, the staff physician in our study reached out to the appropriate medical specialists for guidance regarding clearance for physiotherapy intervention. There was no sample size restriction for this study, and participants were chosen using purposive convenience sampling. This study was approved by the Research Ethics Board (REB #1000076914) at our institution.

2.2. Participant recruitment

The study was introduced to families by a metabolic staff physician in the LSD clinic during the child's regular follow-up appointment. Additionally, a recruitment package that included a study recruitment letter, the study consent form, and the assent form was sent to all eligible families by mail. The registered physiotherapist working in the LSD clinic then contacted families by telephone for a screening interview to explain the study's purpose and determine their interest in the study. For those interested in participating, the physiotherapist scheduled an initial appointment visit and sent a subsequent email with appointment details and a copy of the study consent and/or assent form. Informed consent and/ if applicable assent were obtained from the caregiver and/or participant as applicable during the initial visit. A copy of each form was securely uploaded to the participant's electronic medical chart. The original physical copies were kept in a locked filing cabinet in a locked office.

2.3. Data collection

Each participant was assessed by the same physiotherapist five times at regular intervals over 12–14 months. The visits lasted 60–90 min and were conducted either virtually or in-person based on participant preference; however, the study team required participants to be seen in-person for their first and last visits to obtain a comprehensive physical exam, including objective measurements of ROM and strength.

At each visit, participants and their caregivers were asked to fill out a PedsQL™ 4.0 Pediatric Quality of Life Inventory™ survey in English (Mapi Research Trust, France) to measure health-related quality of life. The physiotherapist reviewed the standardized instructions for the PedsQL™ survey with families. The ‘Parent Report’ questionnaire was filled out by caregivers. Participants who were cognitively able completed the PedsQL™ questionnaire that corresponded with their age group. A medical interpreter was present, if required to provide translation services during PT appointments.

The physiotherapist designed and used a PT assessment form (Appendix A) to collect information on pain, ROM, strength, balance, and function. ROM was measured using a transparent plastic goniometer with a 360-degree head and 12-in. arms (Baseline® Evaluation Instruments, Fabrication Enterprises Inc., NY, USA). Strength was assessed using manual muscle testing (MMT) following the Kendall Muscle Grading System [6]. Assessments were documented securely in the patient's electronic medical chart. Function was determined based on subjective reports of activity endurance (e.g., ambulation, stairs, bicycle riding) and participation in extra-curricular activities (e.g., dance, ball sports, swimming).

At the end of each visit, participants received printed and digital copies of their individualized home exercise program (HEP) tailored to their needs based on assessment findings. Between visits, the physiotherapist conducted brief telephone follow-ups with parents each month to ensure safety and compliance with the HEPs. These discussions also allowed an opportunity for adjustments to be made to HEPs if needed. The physiotherapist remained available to participants and their families by phone or email throughout the study.

2.4. Data analysis

Descriptive analytics were used to describe the study data. To illustrate PedsQL™ data, we first obtained ordinal raw data from questionnaires, then followed PedsQL™ scoring instructions to reverse-score and linearly transform the items to a scale out of 100. This reverse scoring allowed for easier data interpretation as higher scores indicated a higher health related QoL. The PedsQL™ questions were listed under four categories, including Physical Functioning (8 items), Emotional Functioning (5 items), Social Functioning (5 items), and School Functioning (5 items). Using Microsoft Excel (Microsoft Canada Inc., Mississauga), we computed the mean in each category to create three scalar scores: Psychosocial Health Summary Score (15 items), Physical Health Summary Score (8 items), and Total Score (23 items). The data was formatted into a clustered column chart using Microsoft Excel to analyze trends for the scalar scores of each participant over time.

The physiotherapist reviewed the participant's PT assessment forms and provided a numerical score of 0–2 to describe whether an individual's ROM was stable (no change since last visit), improved, or worsened compared to their previous assessment. This method of scoring was repeated for strength, pain, function, and balance. The data was plotted into a stacked bar chart using Microsoft Excel to depict study outcomes.

3. Results

3.1. Participant characteristics

Data was collected from physiotherapy visits from September 2021 to April 2023. Children were between 5 and 16 years old at the time of enrollment and were diagnosed with either MPS I (MPSIH or MPSIA), MPS II, or MPS III. A total of 21 patients were eligible for enrollment in our study center. Of those, 7 families declined enrollment. Reasons included: 1) perceived large time commitment, 2) distance from study center (two families), 3) Caregiver uncertainty regarding potential benefit of PT services, given the patient was fully mobile with no range of motion restrictions, 4) inability to reach caregivers.

We recruited 15 participants (Table 1), of which 7 completed the entire study, and 8 were unenrolled during the study. Reasons for unenrollment included loss to follow-up, caregiver request due to other responsibilities, or poor feasibility of the study due to participant location from the study center.

Table 1.

Participant characteristics.

Characteristic	N
Sex
Female	6
Male	9
Age at time of enrollment
Young Children 5–7 years old	3
Children 8–12 years old	8
Teenagers 13–18 years old	4
MPS Subtype  MPS IH or I-A  MPS II  MPS III	7 5 3
Reason for unenrollment
Lost to follow-up	4
Caregiver request	3
Distance from study center	1

3.2. Adverse events

Participants experienced adverse events during the study, but these were considered mild/moderate and were unrelated to the study intervention.

3.3. Participants who completed the study

Out of seven participants who completed the study, five were diagnosed with MPS Type I and two had MPS Type II.

3.3.1. PedsQL™ surveys

PedsQL™ data was obtained at each visit. Five participants were able to complete the self-reported PedsQL™ surveys. As shown in Fig. 1, PedsQL™ caregiver proxy-report ‘Total Scale’ scores improved for all participants when comparing their initial and final visits. The same trend was observed for the participant self-reported scores, except for Participant 7. ‘Physical Health’ and ‘Psychosocial Health’ summary scores followed the same pattern as the total scores, with no obvious trend between the two when comparing scores at each visit. (Appendix B).

Fig. 1.

Clustered column chart representing PedsQL™ total scale scores at visit 1–5 for each participant who completed the entire study.

3.3.2. Presence of pain at each visit

As shown in Fig. 2, two participants reported pain at all five follow-up physiotherapy visits. One participant had pain at 80% of their visits, three participants had pain at 60% of their visits, and one had pain at 40% of their visits.

Fig. 2.

Percentage of visits during which participant or caregiver-proxy reports indicated the presence of pain among participants who completed the entire study.

3.3.3. PT assessment outcomes and goals

Fig. 3 shows that PT outcomes measures, which included function, strength, balance, ROM, and pain, were either stable or improved for the majority of participants. One individual presented with decreased function at the end of the study. Two participants had worsened pain and ROM at the end of the study.

Fig. 3.

Horizontal bar chart outlining physiotherapy assessment outcomes at visit #5 (end of study) for the seven participants who completed the entire study.

Physiotherapy goals were discussed with the participants and their caregivers during each visit. By the end of the study, four had met all their goals, one met 4 out of 5 of their goals, one met 2 out of 5 of their goals. One individual's goals were not reviewed during their final visit. The physiotherapist reached out to the participant's parents but did not receive a response from them.

3.4. Participants who were unenrolled

Out of eight participants who were unenrolled, two had MPS Type I, three had MPS Type II, and three had MPS Type III.

3.4.1. PedsQL™ surveys

As described in Fig. 4, the participants who were unenrolled from the study completed three physiotherapy visits or less. Four participants had either the same or higher ‘Total Scale’ PedsQL™ scores between the initial and last visits. The other three participants only completed one PedsQL™ survey, therefore there was not enough data to compare changes.

Fig. 4.

PedsQL™ total scale scores for participants who were unenrolled from the study before completing all five physiotherapy visits.

3.4.2. Physiotherapy assessments

There was insufficient data for three of the eight participants, as they only completed one visit. The other five participants had stable or improved findings for pain, ROM, balance, and strength. Function remained stable for all, except for one participant. (Appendix C)

4. Discussion

Our study has built on previous research exploring the role of PT services for individuals with MPS. Firstly, our results showed that offering PT intervention regularly was safe and did not harm our participants. Secondly, most of those who completed the study had MPS Type IH or MPS Type I-A. In contrast, those with MPS Type III were all unenrolled prior to completing it. Thirdly, all participants, including some of those who were unenrolled, had improved QoL when comparing first and final study visits, with the exception of one individual. In addition, the majority of those who completed at least two visits showed either stable or improved physiotherapy outcomes. Lastly, this study demonstrates the importance of considering pain and discussing physiotherapy goals when providing PT treatment to pediatric patients with MPS. Overall, these findings help to understand the effect of physiotherapy on QoL, pain, and function for children with MPS.

4.1. PT & MPS subtypes

Most participants found benefit in being seen regularly by a physiotherapist; however, just over half of them were unenrolled early from the study. Of note, all three participants with MPS Type III (Sanfilippo Syndrome) were withdrawn during the study, either due to loss-to-follow-up or at their parents' request due to competing responsibilities. Participants in our study who were impacted by significant neurodegenerative disease were limited in their ability to participate consistently during PT appointments and with parents at home while completing their HEPs. It has previously been shown that the cognitive challenges and behaviour difficulties associated with MPS Type III, including hyperactivity, unpredictable aggressive behaviour, and agitation, place increased load on caregiving demands [7]. It has also been found that these families already manage a high level of stress [7], which could explain the parents' requests to unenroll their child from our study. Caregivers of children with MPS III were motivated and engaged during PT sessions in our study; however, other medical appointments, caregiving for siblings, and pandemic-related circumstances contributed to inconsistent follow-through. We should also mention that our results could have been skewed due to the small number (three patients) diagnosed with MPSIII that participated in this study. The frequency of physiotherapy visits every 3 months in our study might have led to higher rates of unenrollment. A recently published guidelines (Muscol et al., 2022) for the management of patients with MPS Type III, noting that regular physical therapy may reduce physical discomfort and support some aspects of mobility in patients diagosed with MPS type III. Physiotherapy can be effective for pain management, bone health, avoidance of pressure sores, and enabling patients to maintain access to their environment. The authors noted that “physical therapy should be considered as early as possible and be performed regularly before, during, and beyond the decline of gross motor skills to maintain mobility and function and reduce development of contractures”. [8]. Therefore, regular physiotherapy intervention is likely beneficial for all children with MPS. The frequency of follow-up visits should be tailored to meet the individual needs of each patient and their family to optimize outcomes and quality of life [8]. PT interventions should focus on pain management, functional mobility and activity endurance. Regardless of MPS subtype, the authors believe that all children with MPS would benefit from being connected with a physiotherapist to monitor strength and ROM, supporting optimal function given the multi-system nature of the disease.

4.2. Health-related QoL

While ERT and HSCT treatments for MPSs have shown benefits to a patient's clinical outcome, they lead to only a partial response in addressing skeletal disease. Ongoing research is being conducted to better understand how these treatments impact patients' QoL and daily living [9]. MPSs are chronic, multifaceted conditions in which pain and decreased activity tolerance reduce independence with mobility, which can result in decreased social connections with others [9]. Our results indicate that PT intervention generally had a positive effect on health-related QoL, which considers both psychosocial and physical aspects. Most participants were able to maintain their function, strength, and range of motion during our study, which allowed them to continue participating in their regular meaningful activities and interactions with others. The decrease in PedsQL score observed for Participant 7 might have been due to the patient undergoing orthopedic surgery prior to the end of the study. This patient's sleep and function were limited by post-operative pain. Williams, Challoumas, and Eastwood have published that although orthopedic surgery might improve QoL and function in children with MPS, there needs to be further research done to include QoL measures in order to confirm this finding [10]. Overall, our findings indicate that supportive adjuncts to MPS treatment, such as physiotherapy, might help to support pediatric patients from a psychological and physical perspective by maintaining their functional abilities.

4.3. Pain

Due to the progressive nature of MPS, this patient population often faces challenges related to chronic pain. Our results support the existing evidence that pain is a prevalent feature of MPS, as participants often reported experiencing pain when asked during their follow-up visits. Chronic pain can lead to anxiety and depression as it can disrupt children's normal activities and routines [11], [12]. Pain has typically been managed with invasive surgical procedures or pharmacologically with opioid and non-opioid analgesics [11], [12]. Interestingly, most of the participants who completed the study described their pain as either stable or improved during their last physiotherapy visit. This might be because PT intervention can improve an individual's confidence with their mobility and can alter perceptions of chronic pain through pain science education, therefore giving patients a sense of control over their pain [11], [13]. As it has been suggested that children might have a more modifiable perception of pain compared to adults, PT intervention has the potential to provide an enjoyable experience to children, which reduces fear around pain by introducing playful activities that promote movement [12], [13]. Range of motion exercises can also help decrease or prevent pain by minimizing the risk of contractures [13]. Ultimately, it seems that a combination of pharmacological and rehabilitative management might be an optimal strategy to manage chronic pain in children with MPS.

4.4. PT assessment outcomes & goals

Maintaining and optimizing function is essential for children living with MPS. Our study supports the idea that physiotherapy intervention can positively impact outcomes such as pain, ROM, balance, strength, and function. By the end of the study, it was apparent that the participants were more confident in their ability to move. This idea is supported by existing literature, which found that physiotherapy can help in chronic conditions with generalized muscle pain by increasing an individual's wellbeing through aerobic and resistance exercises [14]. The HEPs provided in this study were tailored to each patient, and physiotherapy goals were created and reviewed during follow-up visits. A study conducted by Ayling Campos, Amaria, Campbell et al. found that most children with chronic pain improve with PT intervention [12]. They also mentioned, however, that some children do not respond despite multiple treatments [12], which supports our study findings that saw some children have decreases in function and increases in pain. Without a cure for MPS, symptom management is a key element in maximizing QoL for a child with this condition, and physiotherapists are in a unique position to monitor ROM, provide guidance on strengthening, discuss pain management strategies, and create HEPs that increase a child's confidence with movement.

5. Limitations

There are a few limitations to our study design. Firstly, the findings should be interpreted with caution due to the small sample size of our study. MPSs are a group of rare diseases, and it will be beneficial to conduct a multicenter study with a bigger patient cohort in the future. Secondly, we were unable to make statistical inferences due to the descriptive nature of the data analysis; however, our results highlight important trends to help us understand the role of PT intervention for children with MPS. Thirdly, this longitudinal study required considerable commitment from families, and several participants were lost to follow-up. We tried minimizing unenrollment rates by offering virtual visits; however, tele-rehabilitation might not always be the most effective method to deliver PT services.

6. Conclusion

We set out to determine the effect of regular PT intervention on QoL, pain, and function over time for children with MPS. Our findings indicate that regular PT intervention is likely beneficial for children with MPS regardless of subtype. The frequency of PT visits might vary among patients and should be tailored to the individual needs of patients and families to provide the most supportive and optimal care. PT intervention might be used as an adjunct to existing therapies, as our study demonstrated that most patients had either stable or improved clinical exams. Providing increased confidence for children diagnosed with rare diseases in their mobility allows them to interact with their environment and maintain their independence with their activities of daily living. Physiotherapists play an essential part in providing patients and families with tools that encourage self-management. This work demonstrates the importance of tailoring specific physiotherapy interventions for patients diagnosed with rare diseases to promote their quality of life.

Future studies might investigate the impact of PT intervention on a larger patient cohort, and the role of Occupational Therapy for children with MPS concerning assessments of fine motor function.

CRediT authorship contribution statement

Jian Dealy: Writing – review & editing, Writing – original draft, Methodology, Formal analysis, Data curation, Conceptualization. Michal Inbar-Feigenberg: Writing – review & editing, Supervision, Methodology, Funding acquisition, Formal analysis, Data curation, Conceptualization.

Informed consent statement

Informed consent was obtained from all subjects involved in the study.

Institutional review board statement

The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board (or Ethics Committee) of our institution (REB #1000076914).

Declaration of generative AI and AI-assisted technologies in the writing process

During the preparation of this work, the author(s) used ChatGPT in order to improve readability and language. After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the publication.

Funding

This work was supported by a donation to the SickKids Foundation, The Hospital for Sick Children, Toronto, Ontario, Canada to cover the salary of the physiotherapist.

Declaration of competing interest

Michal Inbar-Feigenberg received research, and consulting funds related to MPSs from pharmaceutical companies, however, these activities are not related to this study. Jian Dealy does not have any conflicts to declare.

Appendix A. Supplementary data

Supplementary Material 1 -Appendix A

Supplementary Material 2 -Appendix B Figure 1 2

Supplementary Material 3 -Appendix C Figure 3

Data availability

Data from this study can be accessed by contacting the corresponding author.