Introduction

Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in children, with an incidence of one in 6,000 male live births [22]. DMD is an X-linked recessive disorder characterized by progressive muscle wasting and weakness. Up to this point, there is no cure for DMD, and treatment is mainly aimed at delaying disease progression and preserving functional abilities. Due to these treatments (including nocturnal ventilation), life expectancy in boys with DMD has increased from 14 years of age in the 1960s to 25 years of age in the 1990s. Currently, the median survival of boys with DMD is estimated to be over 30 years [8, 16].

To improve care for DMD patients and to develop tailored training and new supportive aids, it is important to gain more insight into the course of the disease and the factors affecting its course. The current literature on disease progression is mostly aimed at the level of muscle or cell structures, and hardly at the level of function or activity [12, 23, 32]. The maintenance of function and activity, however, is highly related to the level of independence and quality of life [24]. Therefore, it is relevant to investigate disease progression from the levels of function and activity as well.

The little knowledge that there is on function and activity in boys with DMD is mainly focused on the lower extremity. Loss of lower extremity function can be compensated fairly well by using a wheelchair; in contrast, upper extremity (UE) function is much harder to support. There are only a few supporting devices for the arms available, and these devices do not cover the full range of function and activity [19]. With the current life expectancy, boys with DMD will live with impaired UE function for more than 15 years. If left unsupported, they may be seriously limited in UE activities and restricted in social participation for the same period of time.

In the literature, little is known about UE function in the course of DMD, especially regarding the execution of complex activities [30]. Understanding the execution of complex activities, e.g., during self-care and domestic life, is essential for the development of therapeutic interventions and supportive aids.

The International Classification of Function, Disability and Health (ICF) presents a framework to describe human functioning at three different levels: the level of body functions and structures, the level of activities, and the level of social participation [26]. The latter two are highly interrelated. The relation between these levels, however, is not linear. Therefore, it is necessary to study upper limb function in a broad perspective, taking all domains of the ICF into account.

The aim of this study was to gain insight into the changing patterns of UE function in the course of DMD by means of an internationally distributed Web-based questionnaire focusing on all levels of the ICF.

Methods

Procedures

A Web-based questionnaire, containing questions on all ICF domains (function, activity, participation), was translated into five languages (English, Dutch, German, Italian, Spanish). This questionnaire was subsequently distributed around the world by contacting Duchenne patients’ organizations worldwide and asking them to send the Internet address of the questionnaire to their members. The full questionnaire can be found in “Appendix”. This procedure was approved by the medical ethical committee in the Arnhem-Nijmegen region (the Netherlands) and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Participants

The questionnaire could be filled in by patients with DMD or their parents or caregivers. Because an anonymous Web-based questionnaire was used in this study, the diagnosis of DMD could not be confirmed by DNA diagnosis. However, to make sure that respondents fitted the clinical Duchenne phenotype, the diagnostic criteria of Emery were used [9]. Based on these criteria, respondents were excluded if the diagnosis was made after the age of 10 and if wheelchair confinement occurred after the age of 13 (when the respondents did not use corticosteroids). In addition, female DMD patients and respondents with the diagnosis of Becker muscular dystrophy (BMD) or any other muscular dystrophy were excluded. Respondents were also excluded if the stage of the disease could not be determined based on their answers.

Outcome measures

Outcomes were categorized in four different categories. Participant characteristics were shown to give insight in the population. Pain and stiffness give insight in the ICF function level, UE activity gives insight in the ICF activity level, and social participation gives insight in the ICF participation level.

Participant characteristics

To see if the population is comparable to the DMD population reported in literature, the following participant characteristics were assessed: age, age of diagnosis, age of wheelchair confinement, corticosteroid use, presence of scoliosis (based on the respondents knowledge, not confirmed by a physician) and the use of assistive devices for the arms.

Pain and stiffness

Questions concerning pain and stiffness were modified from the University of Michigan Upper Extremity Questionnaire [28]. Three different aspects of pain and stiffness were assessed: frequency (range, 0–6), severity (range, 0–10) and limitations due to pain and stiffness (range, 0–10). Pain and stiffness combination scores were calculated by taking the sum of the frequency, severity and limitation scores for pain and stiffness, respectively (range, 0–26). The percentage of respondents that experience pain was set at a combination score larger than 1.

UE activity

Items at the level of activities were chosen from existing measures used in clinical practice and were based on the study by van Beek et al. (submitted) [30]. They concluded that the Capabilities of Upper Extremity questionnaire (CUE) [18] and the ABILHAND questionnaire [31] are the most applicable self-report instruments to investigate the upper extremity activity level in teenage boys with DMD. The CUE examines basic UE mobility activities. In addition, the ABILHAND examines complex UE activities. Next to the 22 ABILHAND items described by Vandervelde et al. [31], four more items were added (i.e., eat with a spoon, use fork and knife, drink a glass of water without straw, and use the keyboard of a computer) because these activities were indicated as very important by boys with DMD [30]. This adapted scale will be referred to as ABILHAND-plus. Furthermore, the Brooke scale [3] was selected as the gold standard for assessing basis UE activity in patients with DMD. Lastly, participants were asked for the three activities that cause the most problems due to UE impairments.

Social participation

Concerning social participation, participants were asked whether they went to school, had a job, practiced sports, had hobbies, performed activities with friends, and/or were involved in a romantic relationship. In addition, the respondents were asked if they experienced UE limitations while performing social activities (5-point scale).

Analysis

For all outcome measures, the total group score was determined as well as the score per disease stage. Four different disease stages were defined based on the guidelines of Bushby et al. [4]: in the early ambulatory stage, walking difficulties are experienced, however, the person is still able to climb stairs; in the late ambulatory stage, the person is still able to walk, but not able to climb stairs; in the early non-ambulatory stage, persons are no longer able to walk, but their UE function is not very limited (Brooke scale 1–2 [3]); and in the late non-ambulatory stage, UE function is increasingly limited (Brooke ≥3).

Descriptive analysis of the data was performed: mean, median, standard deviation, and frequency tables were calculated if applicable. When the participants did not fully complete the questionnaire, all available items were included in the analysis. Wilcoxon rank-sum tests for independent groups were used to compare differences in pain and stiffness between the preferred and non-preferred side. All statistical analyses were done using IBM SPSS Statistics version 20 for Windows (IBM, Somers, NY, USA).

Results

Participant characteristics

In total, 344 participants from 14 different countries (Italy, the Netherlands, England, Spain, USA, Germany, Belgium, Switzerland, Canada, Ireland, Australia, Nepal, Peru, and India) answered the questionnaire, of which 131 were excluded based on the exclusion criteria. From the 213 remaining participants, 198 filled in the complete questionnaire, whereas 15 participants filled in the questionnaire only partially. Table 1 shows the participant characteristics.

Table 1 Participant characteristics
Full size table

Pain and stiffness

The pain and stiffness combination scores ranged between 0 and 26 (26 = maximum possible score). No differences were found between the preferred and non-preferred side. Pain was most frequently present the shoulders, while stiffness was most frequently present in the fingers. Pain levels gradually increased with disease stage, while stiffness levels increased most in the late non-ambulatory stage (Fig. 1; Table 2). In Table 2, the pain and stiffness levels of the preferred and non-preferred side are combined.

Fig. 1
figure 1

Average pain and stiffness combination scores per body segment

Full size image
Table 2 Pain and stiffness
Full size table

UE activity

Forty-four percent of the respondents in the early ambulatory stage reported limitations while performing the basic activities of the CUE. In addition, 25 % of the respondents in the early ambulatory stage reported that it was difficult or impossible to perform some of the daily activities from the ABILHAND-plus. These percentages increase to 95 and 90 %, respectively, in the late non-ambulatory stage (Table 3).

Table 3 Activity limitations (Brooke, CUE, ABILHAND-plus) per disease stage
Full size table

Overall, the activity “eat and preparing food” was experienced most problematic. However, in the ambulatory stages the activities “get dressed”, “reach to objects/lift objects” and “write” were mentioned more often, while in the non-ambulatory stages “personal hygiene”, “drink”, and “use the computer” were mentioned most next to the activity “eat and preparing food” (Table 4).

Table 4 Activities that cause the most problems in daily life due to UE impairments
Full size table

Social participation

Restrictions in social participation increased with increased disease stage. The percentage of respondents that experience UE limitations when performing social activities increases with the stage of the disease (Table 5).

Table 5 Social participation per disease stage
Full size table

Discussion

This study showed that activity limitations of the upper extremity in DMD already occur in the early ambulatory phase, and increase with more advanced stages of the disease. In addition, pain and stiffness increase with more advanced disease stages and restrictions in participation are more frequently present in more advanced disease stages.

Participant characteristics

The respondents in this study were between 1 and 37 years old and comprised DMD patients in all stages of the disease. Age of diagnosis, age of being wheelchair confined, prevalence of scoliosis, and corticosteroid use were comparable to the results reported in literature [5, 16, 20, 21].

The use of splints and supportive devices for the arms was around 9 %. However, the percentage of participants that reported having difficulties using their UE was much larger. A Brooke scale of 1 was reported by merely 34 % of the respondents, indicating that 66 % of the boys already experienced some activity limitations, even in an early stage of the disease. Only a small percentage of the participants that experienced upper extremity limitations used an arm support. This finding is in contrast with the lower extremity, where splints are highly recommended and used. The non-frequent use of arm supports could be caused by the fact that arm supports do not give natural support or that the arm supports are too prominent. Both invisibility and the ability to give natural support are important for orthotics to be worn in daily life [27].

Pain and stiffness

In total, 35.6 % of the respondents experienced pain in their UE more than a few times a month; in adults this percentage was 55.4 %. These numbers are comparable with the literature, where percentages between 4.3 and 54 % have been reported [10, 29, 33].

Pain combination scores gradually increased in the more advanced disease stages. The average pain and stiffness combination scores are relatively low (Fig. 1). This is probably due to the large number of respondents that do not experience pain or stiffness. The pain combination scores of the respondents that did experience pain ranged from 1 to 21 and the stiffness combination scores ranged from 1 to 26. No other studies on the relation between pain and disease progression in DMD were found. Stiffness also appeared to increase with the stage of the disease, which is in correspondence with Cornu et al. [7]. They, however, measured the stiffness in the joint, whereas we assessed the subjective experience of joint stiffness.

Overall, pain was most severe in the shoulders. This is in accordance with the results of Engel et al. [10] and Tifferau et al. [29]. Stiffness was most severe in the fingers. One explanation for this could be that the participants were still able to use their fingers in a relatively late stage of the disease, while the shoulder and elbow could not be moved anymore, making patients probably less aware of the stiffness in their shoulders.

UE activity

The Brooke scale is the most commonly used instrument to evaluate the upper limb activity level in boys with DMD. The CUE has never been used in boys with DMD. The ABILHAND has been validated in boys with DMD [31]; and van Opstal et al. [25] used the ABILHAND to measure the capacity to manage daily activities that require the use of the upper limb. They also divided the results for the different disease stages (“ambulant”, “nonambulant, relatively good arm abilities”, and “nonambulant, decreased arm abilities”). The scores per items were not shown in this study, however the total score indicated that arm function decreases with disease stage. This is comparable to the results of this study.

The ABILHAND has been validated in children older than 6 years, the CUE has only been used in adult subjects. Since 23 participants were under the age of 6 years and 175 participants were under the age of 18 years, it could be that some activities in the CUE and ABILHAND are not valid for the participants. The CUE, however, consists of basic activities that were considered as not very age-specific, therefore age was not expected to be a limiting factor to perform the CUE activities. The ABILHAND consists of more complex activities, which could be more difficult to perform by very young children. For example, the activities “cut nails”, “open a pack of chips” and “open a pack of biscuits” are pointed out more difficult in the early ambulatory stage compared to the late ambulatory stage. This is probably due to the fact that the children in the early ambulatory stage (median age, 7.2 years) are too young to be able to perform the item without difficulties.

Regarding the CUE, item 12 (holding an object like a hammer with your hand) was erroneously not included in the questionnaire. This, however, did not influence the remaining results of the CUE, since we looked at the separate items and not at the total score.

The scores on the reported Brooke scale increased with age. The median age at which UE activity level started to deteriorate (Brooke 2) was 11.4 years. This result is comparable to the results of Jung et al. who found that the median age of Brooke scale 2 was around 10 years [15], and to Lord et al. [17] who found a median age around 11 years.

The Brooke scale gives a stepwise insight into UE activity, whereas CUE and ABILHAND-plus provide us with a more detailed description of the activity limitations related to the UE. Items from the CUE as well as the ABILHAND-plus are already difficult in the early ambulatory stage. This indicates that difficulties performing upper extremity tasks occur already long before boys with DMD lose the ability to walk. These early activity limitations related to UE impairments have not been reported before.

Social participation

Restricted social participation is a huge problem in boys with DMD [13]. This can result in reduced engagement in social activities, social withdrawal, or even social isolation [4]. The results of this study show that 95.1 % of the respondents between 5 and 20 years went to school or attended other classes, which is comparable to the worldwide population in developed countries where 95.9 % of children attend school [1]. Of the respondents over 20 years of age, 34.8 % worked and 26.1 % of the respondents over 20 years of age still attended school. In the healthy population of the same age, over 80 % of the people are employed or have education [6].

Of all the boys with DMD, 37 % participated in sports and 7.4 % of the adults reported having a romantic relationship. These percentages are lower than in the healthy (adult) population worldwide [11, 14]. In comparison, Bendixen et al. [2] stated that boys with DMD showed less participation in the physical domain, but not in the recreational and social domains. The results of the current study, however, showed that participation in boys with DMD was also restricted in these other domains. This difference can be explained by the applied measurement instruments. Bendixen et al. [2] used the children’s assessment of participation and enjoyment (CAPE), while we used open questions. In addition, the participants of the study by Bendexen et al. [2] were between 5 and 15 years of age, whereas the population also included boys older than 15 years. Older boys are expected to have more participation restrictions, since they have more UE impairments. This is confirmed by the results in Table 5, where about 70 % of the respondents report experiencing mild or severe UE limitations when performing social activities and these percentages tend to increase with disease stage.

Conclusions

Pain, stiffness, activity limitations, and social participation restrictions are higher in more advanced disease stages. However, they are already present in the early ambulatory stage. About 70 % of the respondents state that they experience UE limitations when performing social activities. Therefore, clinicians should already pay attention to upper limb activity limitation before the DMD patients lose their capacity to walk. Effective and adequate aids as well as attention for pain and stiffness in the therapeutic management could help to reduce UE activity limitations and related restrictions in social participation.