Acceptability, validity and responsiveness of inertial measurement units for assessing motor recovery after gene therapy in infants with early onset spinal muscular atrophy: a prospective cohort study.

BACKGROUND: Onasemnogene abeparvovec gene replacement therapy (GT) has changed the prognosis of patients with spinal muscular atrophy (SMA) with variable outcome regarding motor development in symptomatic patients. This pilot study evaluates acceptability, validity and clinical relevance of Inertial Measurement Units (IMU) to monitor spontaneous movement recovery in early onset SMA patients after GT. METHODS: Clinical assessments including CHOPINTEND score (the gold standard motor score for infants with SMA) and IMU measurements were performed before (M0) and repeatedly after GT. Inertial data was recorded during a 25-min spontaneous movement task, the child lying on the back, without (10 min) and with a playset (15 min) wearing IMUs. Two commonly used parameters, norm acceleration 95th centile (||A||_95) and counts per minute (||A||_CPM) were computed for each wrist, elbow and foot sensors. RESULTS: 23 SMA-patients were included (mean age at diagnosis 8 months [min 2, max 20], 19 SMA type 1, three type 2 and one presymptomatic) and 104 IMU-measurements were performed, all well accepted by families and 84/104 with a good child participation (evaluated with Brazelton scale). ||A||_95 and ||A||_CPM showed high internal consistency (without versus with a playset) with interclass correlation coefficient for the wrist sensors of 0.88 and 0.85 respectively and for the foot sensors of 0.93 and 0.91 respectively. ||A||_95 and ||A||_CPM were strongly correlated with CHOPINTEND (r for wrist sensors 0.74 and 0.67 respectively and for foot sensors 0.61 and 0.68 respectively, p-values < 0.001). ||A||_95 for the foot, the wrist, the elbow sensors and ||A||_CPM for the foot, the wrist, the elbow sensors increased significantly between baseline and the 12 months follow-up visit (respective p-values: 0.004, < 0.001, < 0.001, 0.006, < 0.001, < 0.001). CONCLUSION: IMUs were well accepted, consistent, concurrently valid, responsive and associated with unaided sitting acquisition especially for the elbow sensors. This study is the first reporting a large set of inertial sensor derived data after GT in SMA patients and paves the way for IMU-based follow-up of SMA patients after treatment.

Efficacy of integrating a semi-immersive virtual device in the HABIT-ILE intervention for children with unilateral cerebral palsy: a non-inferiority randomized controlled trial.

BACKGROUND: The implementation of virtual devices can facilitate the role of therapists (e.g., patient motivation, intensity of practice) to improve the effectiveness of treatment for children with cerebral palsy. Among existing therapeutic devices, none has been specifically designed to promote the application of principles underlying evidence-based motor skill learning interventions. Consequently, evidence is lacking regarding the effectiveness of virtual-based sessions in motor function rehabilitation with respect to promoting the transfer of motor improvements into daily life activities. We tested the effectiveness of implementing a recently developed virtual device (REAtouch®), specifically designed to enable the application of therapeutic motor skill learning principles, during a Hand Arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) intervention. METHODS: Forty children with unilateral cerebral palsy (5-18 years; MACS I-III; GMFCS I-II) were randomly assigned to a control group or a "REAtouch®" experimental group for a 90-h HABIT-ILE day-camp intervention (two weeks). Children in the REAtouch® group spent nearly half of their one-on-one therapeutic time using the REAtouch®. Participants underwent three testing sessions: the week before (T1), after intervention (T2), and at three months follow-up (T3). The primary outcome was the Assisting Hand Assessment (T3-T1; blinded). Secondary outcomes measured uni-bimanual hand function, stereognosis, gait endurance, daily life abilities, and functional goals. Accelerometers and a manual report of daily activities served to document therapeutic dosage and treatment characteristics. We used one-way RMANOVA to compare the efficacies of the two interventions, and non-inferiority analyses to contrast changes in the "REAtouch®" group versus the "HABIT-ILE" control group. RESULTS: We found significant improvements in both groups for most of the outcome measures (p < 0.05). There was significant non-inferiority of changes in the REAtouch® group for upper extremities motor function, functional goals attainment, and abilities in daily life activities (p < 0.05). CONCLUSIONS: Use of the REAtouch® device during HABIT-ILE showed non-inferior efficacy compared to the conventional evidence-based HABIT-ILE intervention in children with unilateral cerebral palsy. This study demonstrates the feasibility of using this virtual device in a high dosage camp model, and establishes the possibility of applying the therapeutic principles of motor skill learning during specifically designed virtual-based sessions. TRIAL REGISTRATION: Trial registration number: NCT03930836-Registration date on the International Clinical Trials Registry Platform (ICTRP): June 21th, 2018; Registration date on NIH Clinical Trials Registry: April 29th, 2019. First patient enrollment: July 3rd, 2018.

Intelligence and Executive Functions: A Comprehensive Assessment of Intellectually Gifted Children.

OBJECTIVE: Executive functions (EFs) play a key role in cognitive and behavioral functioning. Their multiple forms and implications for daily life behaviors mean they are sometimes equated with intelligence. Several elements even suggest that intellectually gifted children (IGC) may present better executive functioning than typical developing children (TDC, children with intelligence in the average range). However, no study has ever completely tested this hypothesis by a comprehensive assessment of EFs in IGC. METHOD: Results of 30 IGC and 35 TDC aged from 6 to 16 years old were compared through a comprehensive assessment of EFs (inhibition, flexibility, and planning), comprising performance-based and daily life measures. RESULTS: IGC did not differ from TDC in EF performance-based measures. However, they scored higher in parents' and some teachers' ratings, suggesting higher indicators of difficulties in daily life. CONCLUSIONS: Contrary to expectations, high intellectual level does not appear to be associated with superior EFs. Surprisingly, parents and teachers of IGC reported more complaints about their executive functioning in everyday life. We put forward different hypotheses to explain this contrast. Further research is needed to better understand this phenomenon, in which neuropsychology has a fundamental role to play.

Determinants of satisfaction with motor rehabilitation in people with cerebral palsy: A national survey in France (ESPaCe).

BACKGROUND: User satisfaction is a key indicator of healthcare quality. OBJECTIVE: We aimed to identify factors associated with satisfaction with motor rehabilitation (MR) in children and adults with cerebral palsy at a national level, using determinants related to patient characteristics, healthcare organisation and practice features. METHODS: This study was part of ESPaCe, a national survey aimed at documenting the views of individuals with cerebral palsy and their families regarding MR services via a questionnaire, developed by a multidisciplinary group. The ESPaCe questionnaire included the Client Satisfaction Questionnaire (CSQ-8), whose total score was the primary outcome of this study. Survey participation was promoted nation-wide. The questionnaire could be completed by the person with cerebral palsy or their main carer. Analysis included the description of determinants across CSQ-8 quartiles and generalised linear modelling of the CSQ-8 score. RESULTS: From June 2016 to June 2017, 1010 eligible participants (354 children, 145 adolescents and 511 adults) responded to the questionnaire, and 750 completed the CSQ-8. Univariate analysis suggested that multiple factors affected satisfaction with MR. On multivariate sequential adjustment, the factors that decreased satisfaction (all P<0.001) were being an adolescent, Gross Motor Function Classification System levels IV/V, frequent pain, receiving physiotherapy in private practice and poor access to a physiotherapist with specific CP training. Factors that increased satisfaction (all P<0.001) were presence of an MR coordinator, exchanges between healthcare professionals, provision of information regarding MR organisation, and goal setting and effective pain management by the physiotherapist. Organisation and practice features improved the predictive ability of patient characteristics (R2=0.40). CONCLUSION: This study suggests that measures to improve the quality of healthcare for individuals with cerebral palsy should focus on improving pain management by the physiotherapist, establishing a therapeutic alliance, and greater provision of CP-specific practice education for healthcare professionals.

Functional, neuroplastic and biomechanical changes induced by early Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (e-HABIT-ILE) in pre-school children with unilateral cerebral palsy: study protocol of a randomized control trial.

BACKGROUND: Cerebral palsy (CP) causes motor, cognitive and sensory impairment at different extents. Many recent rehabilitation developments (therapies) have focused solely on the upper extremities (UE), although the lower extremities (LE) are commonly affected. Hand-arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) applies the concepts of motor skill learning and intensive training to both the UE and LE. It involves constant stimulation of the UE and LE, for several hours each day over a 2-week period. The effects of HABIT-ILE have never been evaluated in a large sample of young children. Furthermore, understanding of functional, neuroplastic and biomechanical changes in infants with CP is lacking. The aim of this study is to carry out a multi-center randomized controlled trial (RCT) to evaluate the effects of HABIT-ILE in pre-school children with unilateral CP on functional, neuroplastic and biomechanical parameters. METHODS: This multi-center, 3-country study will include 50 pre-school children with CP aged 1-4 years. The RCT will compare the effect of 50 h (two weeks) of HABIT-ILE versus usual motor activity, including regular rehabilitation. HABIT-ILE will be delivered in a day-camp setting, with structured activities and functional tasks that will be continuously progressed in terms of difficulty. Assessments will be performed at 3 intervals: baseline (T0), two weeks later and 3 months later. Primary outcomes will be the Assisting Hand Assessment; secondary outcomes include the Melbourne Assessment-2, executive function assessments, questionnaires ACTIVLIM-CP, Pediatric Evaluation of Disability Inventory, Young Children's Participation and Environment Measure, Measure of the Process of Care, Canadian Occupational Performance Measure, as well as neuroimaging and kinematics measures. DISCUSSION: We expect that HABIT-ILE will induce functional, neuroplastic and biomechanical changes as a result of the intense, activity-based rehabilitation process and these changes will impact the whole developmental curve of each child, improving functional ability, activity and participation in the short-, mid- and long-term. Name of the registry: Changes Induced by Early HABIT-ILE in Pre-school Children With Uni- and Bilateral Cerebral Palsy (EarlyHABIT-ILE). TRIAL REGISTRATION: Trial registration number: NCT04020354-Registration date on the International Clinical Trials Registry Platform (ICTRP): November 20th, 2018; Registration date on NIH Clinical Trials Registry: July 16th, 2019.

4D in vivo quantification of ankle joint space width using dynamic MRI.

Spatio-temporal evolution of joint space width (JSW) during motion is of great importance to help with making early treatment plans for degenerative joint diseases like osteoarthritis (OA). These diseases can affect people of all ages leading to an acceleration of joint degeneration and to limitations in the activities of daily living. However, only a few studies have attempted to quantify the JSW from moving joints. In this paper, we present a generic pipeline to accurately determine the changes of the JSW during the joint motion cycle. The key idea is to combine spatial information of static MRI with temporal information of low-resolution (LR) dynamic MRI sequences via an intensity-based registration framework, leading to a high-resolution (HR) temporal reconstruction of the joint. This allows the temporal JSW to be measured in the HR domain using an Eulerian approach for solving partial differential equations (PDEs) inside a deforming inter-bone area where the HR reconstructed bone segmentations are considered as temporal Dirichlet boundaries. The proposed approach has been applied and evaluated on in vivo MRI data of five healthy children to non-invasively quantify the spatio-temporal evolution of the JSW of the ankle (tibiotalar joint) during the entire dorsi-plantar flexion motion cycle. Promising results were obtained, showing that this pipeline can be useful to perform large-scale studies containing subjects with OA for different joints like ankle and knee.

Temporal resolution enhancement of dynamic MRI sequences within a motion-based framework.

Dynamic MRI has made it possible to non-invasively capture the moving human joints in vivo. Real-time Fast Field Echo (FFE) sequences have the potential to reduce the effect of motion artifacts by acquiring the image data within a few milliseconds. However, the short acquisition times affect the temporal resolution of the acquired sequences. In this paper, we propose a post-processing technique to reconstruct the missing frames of the sequence given the reduced amount of acquired data, which leads to recover the entire joint trajectory outside the MR scanner. To do this, we generalize the Log-Euclidean polyrigid registration framework to deal with dynamic three-dimensional articulated structures by adding the time as fourth dimension : we first estimate the rigid motion of each bone from the acquired data using linear intensity-based registration. Then, we fuse these local transformations to compute the non-linear joint deformations between successive images using a spatio-temporal log-euclidean polyrigid framework. The idea is to reconstruct the missing time frames by interpolating the realistic joint deformation fields in the domain of matrix logarithms assuming the motion to be consistent over a short period of time. The algorithm has been applied and validated using dynamic data from five children performing passive ankle dorsi-plantar flexion.

Neurotomy of the rectus femoris nerve: Short-term effectiveness for spastic stiff knee gait: Clinical assessment and quantitative gait analysis.

BACKGROUND: Stiff knee gait is a troublesome gait disturbance related to spastic paresis, frequently associated with overactivity of the rectus femoris muscle in the swing phase of gait. OBJECTIVE: The aim of this study was to assess the short-term effects of rectus femoris neurotomy for the treatment of spastic stiff-knee gait in patients with hemiparesis. PATIENTS AND METHODS: An Intervention study (before-after trial) with an observational design was carried out in a university hospital. Seven ambulatory patients with hemiparesis of spinal or cerebral origin and spastic stiff-knee gait, which had previously been improved by botulinum toxin injections, were proposed a selective neurotomy of the rectus femoris muscle. A functional evaluation (Functional Ambulation Classification and maximal walking distance), clinical evaluation (spasticity - Ashworth scale and Duncan-Ely test, muscle strength - Medical Research Council scale), and quantitative gait analysis (spatiotemporal parameters, stiff knee gait-related kinematic and kinetic parameters, and dynamic electromyography of rectus femoris) were performed as outcome measures, before and 3 months after rectus femoris neurotomy. RESULTS: Compared with preoperative values, there was a significant increase in maximal walking distance, gait speed, and stride length at 3 months. All kinematic parameters improved, and the average early swing phase knee extension moment decreased. The duration of the rectus femoris burst decreased post-op. CONCLUSION: This study is the first to show that rectus femoris neurotomy helps to normalise muscle activity during gait, and results in improvements in kinetic, kinematic, and functional parameters in patients with spastic stiff knee gait.

Pathological and physiological muscle co-activation during active elbow extension in children with unilateral cerebral palsy.

OBJECTIVE: To address the roles and mechanisms of co-activation in two flexor/extensor pairs during elbow extension in children with cerebral palsy (CP). METHODS: 13 Typically Developing (TD) and 13 children with unilateral spastic CP performed elbow extension/flexion at different speeds. Elbow angle and velocity were recorded using a 3D motion analysis system. The acceleration and deceleration phases of extension were analyzed. Co-activation of the brachioradialis/triceps and biceps/triceps pairs was computed for each phase from surface electromyographic signals. Statistical analysis involved linear mixed effects models and Spearman rank correlations. RESULTS: During the acceleration phase, there was strong co-activation in both muscle pairs in the children with CP, which increased with speed. Co-activation was weak in the TD children and it was not speed-dependent. During the deceleration phase, co-activation was strong and increased with speed in both groups; co-activation of brachioradialis/triceps was stronger in children with CP, and was negatively correlated with extension range and positively correlated with flexor spasticity. CONCLUSIONS: Abnormal patterns of co-activation in children with CP were found throughout the entire movement. Co-activation was specific to the movement phase and to each flexor muscle. SIGNIFICANCE: Co-activation in children with CP is both physiological and pathological.

A new parametrization of the Stillinger-Weber potential for an improved description of defects and plasticity of silicon.

A new parametrization of the widely used Stillinger-Weber potential is proposed for silicon, allowing for an improved modelling of defects and plasticity-related properties. The performance of the new potential is compared to the original version, as well as to another parametrization (Vink et al 2001 J. Non-Cryst. Solids, 282 248), in the case of several situations: point defects and dislocation core stability, threshold displacement energies, bulk shear, generalized stacking fault energy surfaces, fracture, melting temperature, amorphous structure, and crystalline phase stability. A significant improvement is obtained in the case of dislocation cores, bulk behaviour under high shear stress, the amorphous structure, and computation of threshold displacement energies, while most of the features of the original version (elastic constants, point defects) are retained. However, despite a slight improvement, a complex process like fracture remains difficult to model.

A survey of medical and paramedical involvement in children with cerebral palsy in Britanny: preliminary results.

AIM: To describe the amount of medical and paramedical involvement in a sample of Breton children with cerebral palsy as a function of the Gross Motor Function Classification System (GMFCS). MATERIALS AND METHODS: This is a transversal descriptive study. All children with cerebral palsy in Brittany were eligible. Parents who accepted to participate were asked to fill in a questionnaire regarding medical and paramedical involvement with their child. RESULTS: One hundred and thirty-three parents participated. 40.6% of the children were level I on the GMFCS, 20.3% II, 12.03% III, 13.53% IV and 13.53% were level V. Thirty-nine percent of the children took at least one medication (of which 43% were antiepileptic drugs). 33.1% of the children had received at least one injection of botulinum toxin within the year. Forty-four percent used a mobility aid. Eighty-five percent of the children had at least one orthotic device, most often a night ankle-foot orthosis. The median number of rehabilitation sessions per week was 3.85 [0.5-11.5]. The frequency and type of sessions were mostly related to the GMFCS level. CONCLUSION: This study reports high levels of medical and paramedical involvement. Studies must attempt to define optimal practice.

Effectiveness of nitrous oxide and analgesic cream (lidocaine and prilocaine) for prevention of pain during intramuscular botulinum toxin injections in children.

AIMS: To evaluate the effectiveness of an analgesic protocol with nitrous oxide and anaesthetic cream (lidocaine and prilocaine, EMLA) for children undergoing botulinum toxin injections. PATIENTS AND METHODS: Prospective study including 51 injection sessions, 34 children with a mean age of 5.94 (range 2-15) and 209 injected muscles. Pain was evaluated with the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS), the Visual Analogue Scale (VAS) and the Face Pain Scale (FPS) for the children and with a VAS for the parents. RESULTS: CHEOPS score for the 51 sessions was 8.50 (S.D. 3.56). Forty-nine percent of scores were above the therapeutic threshold of 9; 25% of the children evaluated the pain above the therapeutic threshold of 3; 44.74% of the parents' estimations exceeded 3. No correlation was found between age, weight, number of injected muscle and CHEOPS score. CONCLUSION: The association of MEOPA and anaesthetic cream is only effective for 50% of children. This is much lower than treatments for other types of acute induced pain in children. Botulinum toxin injections and cerebral palsy children present certain specificities which require improvements in this analgesic protocol.