Explore the vast range of titles available.

Background Pompe disease is a rare, progressive metabolic myopathy. The aim of this study is to investigate the associations of physical outcomes with patient-reported outcome measures (PROMs) in late-onset Pompe disease. Methods We included 121 Dutch adult patients with Pompe disease. Physical outcomes comprised muscle strength (manual muscle testing using Medical Research Council [MRC] grading, hand-held dynamometry [HHD]), walking ability (6-min walk test [6MWT]), and pulmonary function (forced vital capacity [FVC] in upright and supine positions). PROMs comprised quality of life (Short Form 36 health survey [SF-36]), participation (Rotterdam Handicap Scale [RHS]) and daily-life activities (Rasch-Built Pompe-Specific Activity [R-PAct] Scale). Analyses were cross-sectional: the time-point before, and closest to, start of Enzyme Replacement Therapy was chosen. Associations between PROMs and physical outcomes were investigated using linear regression models. Results RHS and R-PAct scores were better in patients with higher FVC supine and upright, HHD, MRC and 6MWT scores, accounting for the effect of sex, disease duration, use of wheelchair and ventilator support. While the SF-36 Physical Component Summary (PCS) was correlated positively with FVC upright, HHD, MRC and 6MWT scores, there was no significant relationship between the SF-36 Mental Component Summary (MCS) and any of the physical outcomes. Conclusions Participation, daily-life activities, and the physical component of quality of life of adult Pompe patients are positively correlated to physical outcomes. This work serves as a first step towards assessing how changes over time in physical outcomes are related to changes in PROMs, and to define the minimal change in physical outcomes required to make an important difference for the patient.

Background In Pompe disease, an inherited metabolic muscle disorder, severe diaphragmatic weakness often occurs. Enzyme replacement treatment is relatively ineffective for respiratory function, possibly because of irreversible damage to the diaphragm early in the disease course. Mildly impaired diaphragmatic function may not be recognized by spirometry, which is commonly used to study respiratory function. In this cross-sectional study, we aimed to identify early signs of diaphragmatic weakness in Pompe patients using chest MRI. Methods Pompe patients covering the spectrum of disease severity, and sex and age matched healthy controls were prospectively included and studied using spirometry-controlled sagittal MR images of both mid-hemidiaphragms during forced inspiration. The motions of the diaphragm and thoracic wall were evaluated by measuring thoracic cranial-caudal and anterior–posterior distance ratios between inspiration and expiration. The diaphragm shape was evaluated by measuring the height of the diaphragm curvature. We used multiple linear regression analysis to compare different groups. Results We included 22 Pompe patients with decreased spirometry results (forced vital capacity in supine position < 80% predicted); 13 Pompe patients with normal spirometry results (forced vital capacity in supine position ≥ 80% predicted) and 18 healthy controls. The mean cranial-caudal ratio was only 1.32 in patients with decreased spirometry results, 1.60 in patients with normal spirometry results and 1.72 in healthy controls ( p  < 0.001). Anterior–posterior ratios showed no significant differences. The mean height ratios of the diaphragm curvature were 1.41 in patients with decreased spirometry results, 1.08 in patients with normal spirometry results and 0.82 in healthy controls ( p  = 0.001), indicating an increased curvature of the diaphragm during inspiration in Pompe patients. Conclusions Even in early-stage Pompe disease, when spirometry results are still within normal range, the motion of the diaphragm is already reduced and the shape is more curved during inspiration. MRI can be used to detect early signs of diaphragmatic weakness in patients with Pompe disease, which might help to select patients for early intervention to prevent possible irreversible damage to the diaphragm.

Objectives To evaluate changes in diaphragmatic function in Pompe disease using MRI over time, both during natural disease course and during treatment with enzyme replacement therapy (ERT). Methods In this prospective study, 30 adult Pompe patients and 10 healthy controls underwent pulmonary function tests and spirometry-controlled MRI twice, with an interval of 1 year. In the sagittal view of 3D gradient echo breath-hold acquisitions, diaphragmatic motion (cranial-caudal ratio between end-inspiration and end-expiration) and curvature (diaphragm height and area ratio) were calculated using a machine learning algorithm based on convolutional neural networks. Changes in outcomes after 1 year were compared between Pompe patients and healthy controls using the Mann-Whitney test. Results Pulmonary function outcomes and cranial-caudal ratio in Pompe patients did not change significantly over time compared to healthy controls. Diaphragm height ratio increased by 0.04 (−0.38 to 1.79) in Pompe patients compared to −0.02 (−0.18 to 0.25) in healthy controls ( p = 0.02). An increased diaphragmatic curvature over time was observed in particular in untreated Pompe patients ( p = 0.03), in those receiving ERT already for over 3 years ( p = 0.03), and when severe diaphragmatic weakness was found on the initial MRI ( p = 0.01); no progression was observed in Pompe patients who started ERT less than 3 years ago and in Pompe patients with mild diaphragmatic weakness on their initial MRI. Conclusions MRI enables to detect small changes in diaphragmatic curvature over 1-year time in Pompe patients. It also showed that once severe diaphragmatic weakness has occurred, improvement of diaphragmatic muscle function seems unlikely. Key Points • Changes in diaphragmatic curvature in Pompe patients over time assessed with 3D MRI may serve as an outcome measure to evaluate the effect of treatment on diaphragmatic function . • Diaphragmatic curvature showed a significant deterioration after 1 year in Pompe patients compared to healthy controls, but the curvature seems to remain stable over this period in patients who were treated with enzyme replacement therapy for less than 3 years, possibly indicating a positive effect of ERT . • Improvement of diaphragmatic curvature over time is rarely seen in Pompe patients once diaphragmatic motion shows severe impairment (cranial-caudal inspiratory/expiratory ratio < 1.4) .

Objectives Pompe disease is a progressive metabolic myopathy for which enzyme replacement therapy (ERT) was approved in 2006. While various publications have examined the effects of ERT in classic-infantile patients and in adults, little has been published on ERT in children with non-classic presentations. Study design This prospective study was conducted from June 1999 to May 2015. Seventeen patients from various countries participated. Outcome measures comprised muscle function (6-minute walk test, quick motor-function test (QMFT)), muscle strength (hand-held dynamometry; manual muscle testing), and lung function (FVC sitting and supine). For each outcome measure, we used linear mixed-effects models to calculate the difference at group level between the start of therapy and 7 years of ERT. Patients’ individual responses over time were also evaluated. Results Eleven males and six females started ERT at ages between 1.1 and 16.4 years (median 11.9 years); 82% of them carried the common c.-32-13T > G GAA gene variant on one allele. At group level, distance walked increased by 7.4 percentage points ( p  < 0.001) and QMFT scores increased by 9.2 percentage points ( p  = 0.006). Muscle strength scores seemed to remain stable. Results on lung function were more variable. Patients’ individual data show that the proportion of patients who stabilized or improved during treatment ranged between 56 and 69% for lung function outcomes and between 71 and 93% for muscle strength and muscle function outcomes. Conclusions We report a positive effect of ERT in patients with childhood Pompe disease at group level. For some patients, new or personalized treatments should be considered.

Aim  To identify the use and utility of language comprehension tests for unintelligible or non‐speaking children with severe cerebral palsy (CP). Method  Severe CP was defined as severe dysarthria (unintelligible speech) or anarthria (absence of speech) combined with severe limited mobility, corresponding to Gross Motor Function Classification System levels IV to V. An electronic search in the databases of PubMed, PsychInfo, Embase, and CINAHL was made of studies published between January 1965 and December 2008. Indexing terms and free‐text terms for ‘cerebral palsy’, ‘language’, and ‘instrumentation’ were used. Studies were included when (1) the focus was to investigate comprehension of spoken language of children (0–18y) with severe CP, and (2) language tests were described. Results  Twelve standardized tests and five experimental instruments were identified. All standardized tests were developed for children without limited mobility. Only the Peabody Picture Vocabulary Test – Revised was frequently used and feasible for older children with severe CP (>9y). The other tests were used occasionally. To establish utility, adaptations of standardized test procedures were necessary. Interpretation  Language comprehension tests for children with severe CP are scarce. A language comprehension test specifically designed for these children is warranted.

Aim  To identify the use and utility of language comprehension tests for unintelligible or non‐speaking children with severe cerebral palsy (CP). Method  Severe CP was defined as severe dysarthria (unintelligible speech) or anarthria (absence of speech) combined with severe limited mobility, corresponding to Gross Motor Function Classification System levels IV to V. An electronic search in the databases of PubMed, PsychInfo, Embase, and CINAHL was made of studies published between January 1965 and December 2008. Indexing terms and free‐text terms for ‘cerebral palsy’, ‘language’, and ‘instrumentation’ were used. Studies were included when (1) the focus was to investigate comprehension of spoken language of children (0–18y) with severe CP, and (2) language tests were described. Results  Twelve standardized tests and five experimental instruments were identified. All standardized tests were developed for children without limited mobility. Only the Peabody Picture Vocabulary Test – Revised was frequently used and feasible for older children with severe CP (>9y). The other tests were used occasionally. To establish utility, adaptations of standardized test procedures were necessary. Interpretation  Language comprehension tests for children with severe CP are scarce. A language comprehension test specifically designed for these children is warranted. Cite this as: Dev Med Child Neurol 52: e267–e277

Background Pompe disease is a rare, progressive metabolic myopathy. The aim of this study is to investigate the associations of physical outcomes with patient-reported outcome measures (PROMs) in late-onset Pompe disease. Methods We included 121 Dutch adult patients with Pompe disease. Physical outcomes comprised muscle strength (manual muscle testing using Medical Research Council [MRC] grading, hand-held dynamometry [HHD]), walking ability (6-minute walk test [6MWT]), and pulmonary function (forced vital capacity [FVC] in upright and supine positions). PROMs comprised quality of life (Short Form 36 health survey [SF-36]), participation (Rotterdam Handicap Scale [RHS]) and daily-life activities (Rasch-Built Pompe-Specific Activity [R-PAct] Scale). Analyses were cross-sectional: the time-point before, and closest to, start of Enzyme Replacement Therapy was chosen. Associations between PROMs and physical outcomes were investigated using linear regression models. Results RHS and R-PAct scores were better in patients with higher FVC supine and upright, HHD, MRC and 6MWT scores, accounting for the effect of sex, disease duration, use of wheelchair and ventilator support. While the SF-36 Physical Component Summary (PCS) was correlated positively with FVC upright, HHD, MRC and 6MWT scores, there was no significant relationship between the SF-36 Mental Component Summary (MCS) and any of the physical outcomes. Conclusions Participation, daily-life activities, and the physical component of quality of life of adult Pompe patients are positively correlated to physical outcomes. This work serves as a first step towards assessing how changes over time in physical outcomes are related to changes in PROMs, and to define the minimal change in physical outcomes required to make an important difference for the patient.