KinectLAB for MFM Evaluation Scale

International audienc

Responsiveness of the Motor Function Measure in Patients With Spinal Muscular Atrophy

Abstract Objective: To assess the ability of the Motor Function Measure (MFM) to detect changes in the progression of spinal muscular atrophy (SMA). Design: Observational, retrospective, multicenter cohort study. Setting: Seventeen departments of pediatric physical medicine. Participants: Volunteer patients with SMA (NZ112) aged 5.7 to 59 years with no treatment other than physical therapy and nutritional or respiratory assistance. Interventions: Not applicable. Main Outcome Measures: The distributions of the MFM scores (total score and 3 subscores) were analyzed per SMA subtype. The relationships between scores and age were studied. The slopes of score changes (reflecting MFM responsiveness) were estimated in patients with at least 6 months' follow-up and 2 MFMs. Hypothetical sample sizes for specific effect sizes in clinical trial scenarios are given. Results: In 12 patients with SMA type 2 and 19 with SMA type 3 (mean AE SD follow-up, 25.8AE19mo), there was a moderate inverse relationship between age and the MFM total score. Patients with less than 6 months' follow-up showed little score changes. Patients with longer follow-ups showed a slow deterioration (À0.9 points/y for type 2 and À0.6 points/y for type 3). Substantial responsiveness was obtained with the MFM Dimension 2 subscore (proximal and axial motricity) in patients with SMA type 2 (standardized response mean [SRM]Z1.29), and with the MFM Dimension 1 subscore (standing and transfers) in patients with SMA type 3 aged 10 to 15 years (SRMZ.94). Conclusions: If further confirmed by larger studies, these preliminary results on the relative responsiveness of the MFM in SMA will foster its use in monitoring disease progression in patients who participate in clinical trials

Two-year efficacy and safety of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy (SMA)

Risdiplam is an oral, survival of motor neuron 2 (SMN2) pre-mRNA splicing modifier approved for the treatment of spinal muscular atrophy (SMA). SUNFISH (NCT02908685) Part 2, a Phase 3, randomized, double-blind, placebo-controlled study, investigated the efficacy and safety of risdiplam in type 2 and non‑ambulant type 3 SMA. The primary endpoint was met: a significantly greater change from baseline in 32-item Motor Function Measure (MFM32) total score was observed with risdiplam compared with placebo at month 12. After 12 months, all participants received risdiplam while preserving initial treatment blinding. We report 24-month efficacy and safety results in this population. Month 24 exploratory endpoints included change from baseline in MFM32 and safety. MFM‑derived results were compared with an external comparator. At month 24 of risdiplam treatment, 32% of patients demonstrated improvement (a change of ≥ 3) from baseline in MFM32 total score; 58% showed stabilization (a change of ≥ 0). Compared with an external comparator, a treatment difference of 3.12 (95% confidence interval [CI] 1.67-4.57) in favor of risdiplam was observed in MFM-derived scores. Overall, gains in motor function at month 12 were maintained or improved upon at month 24. In patients initially receiving placebo, MFM32 remained stable compared with baseline (0.31 [95% CI - 0.65 to 1.28]) after 12 months of risdiplam; 16% of patients improved their score and 59% exhibited stabilization. The safety profile after 24 months was consistent with that observed after 12 months. Risdiplam over 24 months resulted in further improvement or stabilization in motor function, confirming the benefit of longer-term treatment

Correction to: Use of MFM-20 to monitor SMA types 1 and 2 patients treated with nusinersen.

peer reviewe

Muscle activation during gait in children with Duchenne muscular dystrophy

The aim of this prospective study was to investigate changes in muscle activity during gait in children with Duchenne muscular Dystrophy (DMD). Dynamic surface electromyography recordings (EMGs) of 16 children with DMD and pathological gait were compared with those of 15 control children. The activity of the rectus femoris (RF), vastus lateralis (VL), medial hamstrings (HS), tibialis anterior (TA) and gastrocnemius soleus (GAS) muscles was recorded and analysed quantitatively and qualitatively. The overall muscle activity in the children with DMD was significantly different from that of the control group. Percentage activation amplitudes of RF, HS and TA were greater throughout the gait cycle in the children with DMD and the timing of GAS activity differed from the control children. Significantly greater muscle coactivation was found in the children with DMD. There were no significant differences between sides. Since the motor command is normal in DMD, the hyper-activity and co-contractions likely compensate for gait instability and muscle weakness, however may have negative consequences on the muscles and may increase the energy cost of gait. Simple rehabilitative strategies such as targeted physical therapies may improve stability and thus the pattern of muscle activity

Leveraging Natural History Data in One- and Two-Arm Hierarchical Bayesian Studies of Rare Disease Progression

peer reviewedThe small sample sizes inherent in rare and pediatric disease settings offer significant challenges for clinical trial design. In such settings, Bayesian adaptive trial methods can often pay dividends, allowing the sensible incorporation of auxiliary data and other relevant information to bolster that collected by the trial itself. Previous work has also included the use of one-arm trials augmented by the participants’ own natural history data, from which the future course of the disease in the absence of intervention can be predicted. Patient response can then be defined by the degree to which post-intervention observations are inconsistent with the predicted “natural” trajectory. While such trials offer obvious advantages in efficiency and ethical hazard (since they expose no new patients to a placebo, anathema to patients or their parents and caregivers), they can offer no protection against bias arising from the presence of any “placebo effect,” the tendency of patients to improve merely by being in the trial. In this paper, we investigate the impact of both static and transient placebo effects on one-arm responder studies of this type, as well as two-arm versions that incorporate a small concurrent placebo group but still borrow strength from the natural history data. We also propose more traditional Bayesian changepoint models that specify a parametric functional form for the patient’s post-intervention trajectory, which in turn allow quantification of the treatment benefit in terms of the model parameters, rather than semi-parametrically in terms of a response relative to some “null” model. We compare the operating characteristics of our designs in the context of an ongoing investigation of centronuclear myopathies (CNMs), a group of congenital neuromuscular diseases whose most common and severe form is X-linked, affecting approximately 1 in 50,000 newborn boys. Our results indicate our two-arm responder and changepoint methods can offer protection against placebo effects, improving power while protecting the trial’s Type I error rate. However, further research into innovative trial designs as well as ongoing dialog with regulatory authorities remain critically important in rare disease research

Métrologie et évaluation fonctionnelle motrice dans les maladies neuromusculaires de l’enfance : Illustrations à partir de la Mesure de Fonction Motrice (MFM) et d’une classification en grades de sévérité d’atteinte fonctionnelle motrice (NM-Score)

Advances in the research and treatment of childhood neuromuscular diseases have led to longer patient survivals. Evaluation is thus required not only in clinical practice for patient follow-up but also in medical research because the results of long-awaited clinical trials are beginning to emerge. A rigorous and appropriate metrology is then necessary because rough estimates or the use of improper assessment tools are no more satisfactory. We summarize here the current knowledge on the metrology applied to motor function assessment of patients with neuromuscular diseases. We propose a review of the literature on the tools available to monitor motor function with detailed analyses of their metrological properties. Developped since 1998, the Motor Function Measure presents interesting properties in terms of validity and reliability. We analyzed its sensitivity to change in different patient populations of adults and children. We then propose, the NM-Score, a classification in levels of severity of motor function decline.Validation studies have confirmed the interest of this score as well as its ease of use, validity,and reproducibility. The NM-Score is able to describe the patients precisely and discriminantly in terms of motor function for standing position and transfers, axial / proximal motor function and distal motor function. Being interested in evaluation and measurement in medicine is a sign of rigor necessary for decision-making regarding vulnerable persons with special need.Les progrès de la recherche et de la prise en charge des maladies neuromusculaires de l’enfance ont prolongé la survie des patients. L’évaluation s’impose donc pour le suivi des patients et aussi en recherche clinique car les premiers essais cliniques tant attendus commencent à paraître. Une métrologie rigoureuse et adaptée est alors indispensable parce qu'il n'est possible ni de se contenter d’une quantification approximative ni d'utiliser des outils non adaptés à des pathologies évolutives. Nous résumons l’état des connaissances sur la métrologie appliquée à l’évaluation fonctionnelle motrice des patients atteints de maladies neuromusculaires et proposons une revue de la littérature sur les outils disponibles avec des analyses précises de leurs propriétés métrologiques. La Mesure de Fonction Motrice, développée à partir de 1998, présente des qualités intéressantes en termes de validité et de fiabilité. Nous avons analysé sa sensibilité au changement dans différentes populations de patients adultes et enfants. Nous proposons ensuite, une classification en grades de sévérité d’atteinte fonctionnelle motrice, le NM-score. Les études de validation ont confirmé son intérêt, sa facilité d'utilisation, sa validité et sareproductibilité. Le NM-Score permet de décrire précisément et de façon discriminante les patients en termes de fonction motrice pour la position debout et les transferts, la motricité axiale ou proximale et la motricité distale. S’intéresser à l’évaluation et à la mesure en médecine, c’est faire preuve d’une rigueur indispensable aux décisions de soins touchant des personnes vulnérables aux besoins spécifiques

Metrology and motor function assessment in childhood neuromuscular diseases : Illustration with the Motor Function Measure (MFM) and a classification in levels of motor function decline severity (NM-Score)

Les progrès de la recherche et de la prise en charge des maladies neuromusculaires de l’enfance ont prolongé la survie des patients. L’évaluation s’impose donc pour le suivi des patients et aussi en recherche clinique car les premiers essais cliniques tant attendus commencent à paraître. Une métrologie rigoureuse et adaptée est alors indispensable parce qu'il n'est possible ni de se contenter d’une quantification approximative ni d'utiliser des outils non adaptés à des pathologies évolutives. Nous résumons l’état des connaissances sur la métrologie appliquée à l’évaluation fonctionnelle motrice des patients atteints de maladies neuromusculaires et proposons une revue de la littérature sur les outils disponibles avec des analyses précises de leurs propriétés métrologiques. La Mesure de Fonction Motrice, développée à partir de 1998, présente des qualités intéressantes en termes de validité et de fiabilité. Nous avons analysé sa sensibilité au changement dans différentes populations de patients adultes et enfants. Nous proposons ensuite, une classification en grades de sévérité d’atteinte fonctionnelle motrice, le NM-score. Les études de validation ont confirmé son intérêt, sa facilité d'utilisation, sa validité et sareproductibilité. Le NM-Score permet de décrire précisément et de façon discriminante les patients en termes de fonction motrice pour la position debout et les transferts, la motricité axiale ou proximale et la motricité distale. S’intéresser à l’évaluation et à la mesure en médecine, c’est faire preuve d’une rigueur indispensable aux décisions de soins touchant des personnes vulnérables aux besoins spécifiques.Advances in the research and treatment of childhood neuromuscular diseases have led to longer patient survivals. Evaluation is thus required not only in clinical practice for patient follow-up but also in medical research because the results of long-awaited clinical trials are beginning to emerge. A rigorous and appropriate metrology is then necessary because rough estimates or the use of improper assessment tools are no more satisfactory. We summarize here the current knowledge on the metrology applied to motor function assessment of patients with neuromuscular diseases. We propose a review of the literature on the tools available to monitor motor function with detailed analyses of their metrological properties. Developped since 1998, the Motor Function Measure presents interesting properties in terms of validity and reliability. We analyzed its sensitivity to change in different patient populations of adults and children. We then propose, the NM-Score, a classification in levels of severity of motor function decline.Validation studies have confirmed the interest of this score as well as its ease of use, validity,and reproducibility. The NM-Score is able to describe the patients precisely and discriminantly in terms of motor function for standing position and transfers, axial / proximal motor function and distal motor function. Being interested in evaluation and measurement in medicine is a sign of rigor necessary for decision-making regarding vulnerable persons with special need

La Qualité de vie des enfants et adolescents porteurs d'une maladie neuromusculaire (revue de la littérature et réflexions)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF