I.J.M. De Groot

Developing outcome measures for pediatric mitochondrial disorders: Which complaints and limitations are most burdensome to patients and their parents?☆

Since some drug intervention effects are only experienced by the patient, organizations such as the Food and Drug Administration prefer clinically meaningful outcome measures. Here, we evaluated which symptoms and limitations in daily life are most burdensome to pediatric patients with mitochondrial disorders and their parents, using two questionnaires. In a study of 78 patients, the most burdensome complaints included fatigue, behavior and speech disturbances, epilepsy and muscle weakness and a high degree of limitations in daily activities was found. Importantly, there was a discrepancy between what symptoms metabolic pediatricians estimated would be most burdensome compared to the patients/caretakers opinion. To include feasible and relevant outcome measures in intervention studies, the experience and opinions of patients and caretakers should therefore be heard.

Health-Related Quality of Life and Its Relation to Disease Severity in Boys With Duchenne Muscular Dystrophy Satisfied Boys, Worrying Parents—A Case-Control Study

The progression of Duchenne muscular dystrophy is expected to negatively influence the patients’ health-related quality of life, but knowledge of the relationship with disease severity is limited. We investigated the relationship between health-related quality of life (KIDSCREEN-52 questionnaire) and disease severity (clinical assessments of body functions and activities) in 40 boys with Duchenne muscular dystrophy (19 ambulant, 21 wheelchair dependent) who were in different phases of the disease and underwent life-limiting events such as the loss of the ability to ambulate and the ability to lift the arms. In addition, we compared boys’ health-related quality of life perceptions with that of their parents. The participants’ health-related quality of life was similar to healthy peers’ and not influenced by disease severity, except for the physical domain. Parents scored much lower than the boys on the KIDSCREEN-52 domains Self Perception, Moods and Emotions, and Bullying. The latter finding needs attention in the management of Duchenne muscular dystrophy.

Normal height and weight in a series of ambulant Duchenne muscular dystrophy patients using the 10 day on/10 day off prednisone regimen

Prednisone treatment delays the progressive course of Duchenne muscular dystrophy. The aim of this study was to determine the influence of the 10 day on/10 day off treatment on height and weight. We retrospectively reviewed the growth and weight charts of Duchenne patients born between 1988 and 2006 (patients between 4 and 9 years old, being able to walk in the home situation). Forty-seven patients were eligible for further analysis and divided into two groups: 33 patients treated with prednisone and 14 non-prednisone treated patients. Results of a median follow-up of 57 months (range 27-146) are described. By using linear mixed models this study demonstrates that height and body mass index in prednisone-treated patients with 10/10 regimen are not significantly different compared to untreated patients. We cautiously conclude that the alternating prednisone regimen has no apparent side effects on weight and height in the ambulatory phase of Duchenne muscular dystrophy.

P.7.15 What can we learn from an assisted bicycle training in a symptomatic girl with Duchenne muscular dystrophy? A case study

In this case study a 9-year old ambulatory symptomatic girl with Duchenne muscular dystrophy participated in a dynamic training. Since the role of exercise is far from clear in both boys and girls with DMD, a recently developed assisted bicycle training was evaluated for its feasibility and effectiveness in this girl. The girl trained at home, 15xa0min with her arms followed by her legs, 5 times a week, for 24xa0weeks. The primary outcomes were the Motor Function Measure, and the Assisted Six-Minute Cycling Test. Secondary outcomes were the Vignos and Brooke scale for lower and upper extremity functioning, timed tests (time to rise from a floor, to rise from a chair, to climb 3 stairs and to walk 10xa0m), the Medical Research Scale scale for muscle strength, and quantitative muscle ultrasound to determine the echo intensity of the biceps brachii muscle, the forearm flexors, the rectus femoris muscle and the tibialis anterior muscle. This case study showed that the assisted bicycle training was feasible and safe. Additionally, we found that no physical deterioration occurred during the training period: she remained stable on the Motor Function Measure and the Assisted Six-Minute Cycling Test. Slight improvements in quantitative muscle ultrasound intensity were found, indicating less fatty infiltration in the muscles. Since there are several indications from this case study that physical training could be beneficial in this population, we recommend further research on the effects of dynamic training in girls with DMD and its relation to the level of dystrophin.

S.P.45 ENERGETIC, a multidisciplinary self-management group program for reconditioning and managing fatigue

Abstract Persons with neurological disorders may experience fatigue and secondary physical de-conditioning. A multidisciplinary team developed a client-centred self-management group program including several components: aerobic training; education about training; education on managing fatigue and implementation of training and energy conservation strategies in daily life. The aim was to evaluate the effectiveness of this individually tailored group program. An uncontrolled pilot study with pre-post and follow up (after 3months) measurements was carried out. Participants had a neurological condition, suffered from lack of energy and were motivated to participate in the 15weeks program. Measurement instruments included Canadian Occupational Performance Measure (COPM), Six Minutes Walking Test (6MWT)), Checklist Individual Strength (CIS), and SF-36. Two groups were evaluated, including 13 participants with different neurological disorders (different neuromuscular disorders n =10, multiple sclerosis n =2, stroke n =1). There was a significant improvement following the program on the COPM performance and COPM satisfaction scores, on the CIS-fatigue, and on the domain health change in the SF-36. The improvement on the 6MWT minute walking test was obvious but not significant. At follow up, there was a slight deterioration in most scores except for health change on the SF-36. However, follow-up scores were still better than before the program. These preliminary positive results regarding the effectiveness of this program lead to improvements of the program. These include more psychological support and more support regarding problems at work. The next step will be setting up a randomized clinical trial and implementation of the program in other settings.

S.P.48 Dysphagia in Duchenne muscular dystrophy: A search for the mechanisms

Abstract The purpose of the study was (1) to determine the underlying mechanisms of dysphagia in boys and adults with Duchenne Muscular Dystrophy (DMD); (2) to describe the clinical course and, (3) to develop mechanism based recommendations for efficient, and safe swallowing. Twenty-four DMD patients, from 6.3 to 41.6xa0years (median 17.28) participated in the study. The group was divided into three subgroups according to stages of DMD : Early and late ambulatory (stage I, N xa0=xa06), Early non-ambulatory (stage II, N xa0=xa07), and Late non-ambulatory (stage III, N xa0=xa011). They were investigated while swallowing liquid, thick liquid and solid food using surface EMG of the submental muscle group and a video fluoroscopic swallow study. Quantitative muscle ultrasound was performed to measure thickness and echo intensity of the anterior belly of the digastric and geniohyoid muscle, and of the longitudinal superior and transverse muscle of the tongue. All outcome parameters showed a significant difference between the three subgroups, with most severe dysphagia in stage III. Echo intensity of the oral muscles revealed a progressive increase from stage II and was significant correlated with signs on the VFSS with solid food in the oral phase and with pharyngeal post swallow residue. Weakness of oral muscles causes piecemeal deglutition and post swallow residue, especially with solid food. Oral muscles are involved in late stages of DMD, which influences swallowing negatively. Based on our results we recommend adjustment of food consistencies, and to drink water after meals to clear the oropharynx.

S.P.14 Exploring arm function in persons with LGMD by means of questionnaires

Abstract Limb-Girdle Muscular Dystrophies (LGMD) mainly involve the pelvic and/or shoulder girdle muscles. One of the major problems is limitations in performing daily activities. The natural course of the disease has been described before, and research is done to investigate functional ability of walking. However, little is known about functional abilities of the arms, which is even more important in performing many daily activities. Clear understanding is essential to improve rehabilitation therapies and for development of new arm supports. The aim of this study is to investigate arm function of people with LGMD on activity level, by using questionnaires. A web-based questionnaire to assess arm function was developed. We used questions from the Brooke scale (grading scale, 1–6), the Capabilities of Upper Extremity questionnaire (CUE) (basic arm functions, 30 items, max score 210, higher score means better function) and Abilhand questionnaire (22 ADL items, max score 44, higher score means lower function). Also questions about disease duration, age, gender were asked. The Dutch patient organization (VSN) distributed the questionnaire. Fifty-one people (age 6–72xa0y) participated in the period August 2011 till February 2012. Preliminary results show that in this group, 33% has Brooke scale 1 and 51% Brooke 2–4. The CUE total median score was 159 (range 60–210), corresponding with 75.7% of the maximum score. The total Abilhand median score was 39 (range 8–44) corresponding with a 88.6% of the maximum score. Especially activities above shoulder level are problematic. Patterns of limitations in arm function are further analyzed as are correlations with disease course, age, and gender. The project McArm is a national Dutch ‘Pieken in de Delta’ project. It is partially funded by: Agentschap.nl, an agency of the Dutch Ministry of Economic Affairs, Agriculture and Innovation, the Province of Noord Brabant and the Province of Limburg.

S.P.13 Exploring arm function in FSHD by means of questionnaires

Abstract Facioscapulohumeral muscular dystrophy (FSHD) is a progressive muscular dystrophy. One of the major problems is limitations in performing daily activities. The natural course of the disease has been described before, and research is done to investigate functional ability of walking. However, little is known about functional abilities of the arms, which are even more important in performing many daily activities. Clear understanding is essential to improve rehabilitation therapies and for development of new arm supports. The aim of this study is to investigate arm function of people with FSHD on activity level, by using questionnaires. A web-based questionnaire to assess arm function was developed. We used questions from the Brooke scale (grading scale, 1–6), the Capabilities of Upper Extremity questionnaire (CUE) (basic arm functions, 30 items, max score 210, higher score means better function) and Abilhand questionnaire (22 ADL items, max score 44, higher score meaning lower function). Also questions about disease duration, age, gender were asked. The Dutch patient organization (VSN) supported with distribution of the questionnaire. Seventy-six people participated (age 13–74xa0y) in the period August 2011 till February 2012. Preliminary results show that from this group, 88% have Brooke 2–4. The CUE total median score was 155 (range 53–210), corresponding with 73.8% of the maximum score. The total Abilhand median score was 38 (range 13–44) corresponding with a 86.4% of the maximum score. Especially activities above shoulder level are problematic. Patterns of limitations in arm function are further analyzed as are correlations with disease course, age, and gender. The project McArm is a national Dutch ‘Pieken in de Delta’ project. It is partially funded by: Agentschap.nl, an agency of the Dutch Ministry of Economic Affairs, Agriculture and Innovation, the Province of Noord Brabant and the Province of Limburg.

D.P.26 3D kinematic and EMG study of the arm function in boys with DMD: A pilot study

Abstract Duchenne muscle dystrophy (DMD) is a muscular disorder characterized by progressive muscle weakness, resulting in loss of functions. With increasing life expectancy, the preservation of functional abilities becomes increasingly important. Good assistive arm supports however are rare and do not support the full range of arm functional abilities. For designing new functional arm support a good knowledge of the pattern of arm function loss is needed. Therefore a new measurement protocol, using 3D kinematics and surface electromyography (sEMG), was developed. Five boys with DMD (12.03xa0years, sd 2.52, range 8–15, Brooke 1–4) and 6 age matched controls participated in this pilot study. Standardized (StM) and non standardized (NStM) single joint movements and ADL activities were examined by means of 3D-Vicon motion analysis in combination with sEMG. Outcome measures were: normalized EMG amplitude, passive range of motion (pROM), active range of motion (aROM) and the absolute difference between pROM and aROM. Patients used significantly more of their maximal muscle capacity to conduct StM and NStM compared to controls, also seen in compensatory muscles. pROM was significantly lower in patients in 4 out of 10 movements. aROM of StM was significantly lower in patients in 5 out of 10 movements and aROM of NStM was significantly lower in 7 out of 10 movements. The difference between pROM and aROM was larger in patients than controls for all shoulder movements. A strong relation between age of patients and muscle capacity as well as aROM was seen. The protocol was found feasible for measuring arm function in boys with DMD. The tool was able to discriminate between patients and controls and also between different stages of the disease. Patients used relatively more muscle capacity to conduct arm movements and have a decreased pROM and aROM with increasing age.

S.P.12 Investigating arm function in boys with DMD by means of an international questionnaire

Abstract Duchenne muscle dystrophy (DMD) is a disorder characterized by progressive muscle weakness, resulting in loss of functions. With increasing life expectancy, the preservation of functional abilities becomes increasingly important. Good knowledge on functional abilities is needed, since this information is important for developing new supportive aids and training strategies. Unfortunately, knowledge on the functional abilities of the upper extremity in boys with DMD is limited. To gain more insight in the arm function of boys with DMD an international questionnaire was distributed. A web-based questionnaire to assess arm function in boys with DMD was developed and distributed around the world (more than 12 countries already participated). Next to questions about the medical history of the patients, arm function was assessed using the Brooke scale (grading scale, 1–6), Capabilities of Upper Extremity questionnaire (CUE) (basic arm functions, 30 items, max score 210, higher score means better function) and ABILHAND (22 ADL items, max score 44, higher score meaning lower function). On 23rd March, 2012, 344 participants had started the questionnaire and 227 participants completed the questionnaire. The mean age of patients was 16.8xa0years (range: 1–44xa0years). Scores on the Brooke scale varied between 1 and 6 and seemed to be related with age. The mean CUE total score was 127 (range: 30–210) and the mean ABILHAND score was 22 (range: 0–44), corresponding with a 50% of the maximum score. On this moment, the questionnaire is still ongoing and the results shown are only a small sample of all outcome measures. The outcome variables will be compared and correlations will be calculated. The main focus will be on the pattern of progressive loss of arm/hand function, the effect of medicine use on functional abilities, pain and stiffness and the on the activities that are most important to DMD patients.