NFL is a marker of treatment response in children with SMA treated with nusinersen

BACKGROUND: Recently, the anti-sense oligonucleotide drug nusinersen was approved for spinal muscular atrophy (SMA) and our aim was to find a response marker for this treatment. METHODS: Twelve children with SMA type 1 and two copies of the SMN2 gene were included in a consecutive single-center study. The children were sampled for CSF at baseline and every time nusinersen was given intrathecally. The neuronal biomarkers NFL and tau and the glial biomarker GFAP were measured. Motor function was assessed using CHOP INTEND. Eleven similarly aged children, who were investigated to rule out neurological or infectious disease, were used as controls. RESULTS: Baseline levels of NFL (4598 ± 981 vs 148 ± 39, P = 0.001), tau (939 ± 159 vs 404 ± 86, P = 0.02), and GFAP (236 ± 44 vs 108 ± 26, P = 0.02) were significantly higher in SMA children than controls. Motor function improved by nusinersen treatment in median 13 points corresponding to 5.4 points per month of treatment (P = 0.001). NFL levels typically normalized ( < 380 pg/ml) between the fourth and fifth doses [- 879.5 pg/mL/dose, 95% CI (- 1243.4, - 415.6), P = 0.0001], tau levels decreased [- 112.6 pg/mL/dose, 95% CI (- 206-7, - 18.6), P = 0.01], and minor decreases in GFAP were observed [- 16.9 pg/mL/dose, 95% CI (- 22.8, - 11.2), P = 0.02] by nusinersen treatment. Improvement in motor function correlated with reduced concentrations of NFL (rho = - 0.64, P = 0.03) and tau (rho = - 0.85, P = 0.0008) but not GFAP. CONCLUSIONS: Nusinersen normalized the axonal damage marker NFL and correlated with motor improvement in children with SMA. NFL may, therefore, be a novel biomarker to monitor treatment response early in the disease course

Diagnosis and management of spinal muscular atrophy : Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder due to a defect in the survival motor neuron 1 (SMN1) gene. Its incidence is approximately 1 in 11,000 live births. In 2007, an International Conference on the Standard of Care for SMA published a consensus statement on SMA standard of care that has been widely used throughout the world. Here we report a two-part update of the topics covered in the previous recommendations. In part 1 we present the methods used to achieve these recommendations, and an update on diagnosis, rehabilitation, orthopedic and spinal management; and nutritional, swallowing and gastrointestinal management. Pulmonary management, acute care, other organ involvement, ethical issues, medications, and the impact of new treatments for SMA are discussed in part 2

Non-affirmative Theory of Education as a Foundation for Curriculum Studies, Didaktik and Educational Leadership

This chapter presents non-affirmative theory of education as the foundation for a new research program in education, allowing us to bridge educational leadership, curriculum studies and Didaktik. We demonstrate the strengths of this framework by analyzing literature from educational leadership and curriculum theory/didaktik. In contrast to both socialization-oriented explanations locating curriculum and leadership within existing society, and transformation-oriented models viewing education as revolutionary or super-ordinate to society, non-affirmative theory explains the relation between education and politics, economy and culture, respectively, as non-hierarchical. Here critical deliberation and discursive practices mediate between politics, culture, economy and education, driven by individual agency in historically developed cultural and societal institutions. While transformative and socialization models typically result in instrumental notions of leadership and teaching, non-affirmative education theory, previously developed within German and Nordic education, instead views leadership and teaching as relational and hermeneutic, drawing on ontological core concepts of modern education: recognition; summoning to self-activity and Bildsamkeit. Understanding educational leadership, school development and teaching then requires a comparative multi-level approach informed by discursive institutionalism and organization theory, in addition to theorizing leadership and teaching as cultural-historical and critical-hermeneutic activity. Globalisation and contemporary challenges to deliberative democracy also call for rethinking modern nation-state based theorizing of education in a cosmopolitan light. Non-affirmative education theory allows us to understand and promote recognition based democratic citizenship (political, economical and cultural) that respects cultural, ethical and epistemological variations in a globopolitan era. We hope an American-European-Asian comparative dialogue is enhanced by theorizing education with a non-affirmative approach

Muscle strength and motor function in neuromuscular disorders. A clinical study of children and adolescents with spinal muscular atrophy, myotonic dystrophy, Duchenne muscular dystrophy and amyoplasia

Aim: The aims of this study were to investigate muscle strength and motor function in children and adolescents with four neuromuscular disorders; 1) spinal muscular atrophy (SMA), 2) myotonic dystrophy (DM), 3) Duchenne muscular dystrophy (DMD and 4) the amyoplasia form of arthrogryposis multiplex congenita. Further: 1) to analyze compensatory maneuvers due to muscle weakness in individuals with SMA, 2) to correlate motor function in individuals with DM with the size of the mutation, 3) to evaluate the long-term side effects and effects on muscle strength, motor function, vital capacity and development of scoliosis in boys with DMD treated with low-dose prednisone, and 4) to investigate how muscle strength and joint contractures affect motor function in individuals with amyoplasia and to relate current status to joint position at birth. Methods: 14 children and adolescents from western part of Sweden with SMA, 42 children and adolescents from western and southern Sweden with DM, 37 boys from western Sweden with DMD and 35 individuals from Sweden with amyoplasia participated in this study. In study 2, a control group of 42 age and gender-matched healthy children and adolescents was investigated. Medical records were reviewed and a clinical examination was performed. Isometric muscle strength was measured with an electronic hand-held dynamometer, contractures with an ordinary goniometer and motor function was assessed according to a scale designed for children with neuromuscular disorders. Results: 1) In children and adolescents with SMA profound muscle weakness was found in all assessed muscle groups compared to normal strength. Proximal weakness was greater than distal and lower limbs were more affected than upper limbs. Walking, transfer from lying or sitting to the standing position, and climbing stairs were possible in some of the individuals, despite marked reduction of muscle strength. Compensatory maneuvers described were reinforcement by using stronger upper limbs or distal muscle groups. 2) Children and adolescents with DM were significantly weaker than healthy controls in a majority of the assessed muscle groups. There was a great variation where some of the individuals had normal muscle strength. A strong correlation was found between motor function score and size of the mutation (rho=-0.743). Jumping, heel-standing and head-lifting in supine were difficult to perform, but few had difficulty in walking, running and stair-climbing. 3) Low-dose prednisolone treatment in boys with DMD delayed the time of loss of ambulation by at least 1.7 years and postponed development of scoliosis and contractures. There were also beneficial effects on muscle strength, motor function and vital capacity. The side effects were mild and long-term treatment was possible.4) In individuals with amyoplasia muscle strength affected motor function to a greater extent than joint contractures, although the joint contractures and joint position at birth also had an impact. Muscle strength was reduced in most of the investigated individuals. There was, however, heterogeneity and some of the patients had normal muscle strength in some of the investigated muscle groups. More attention should be paid at developing muscle strength, with early stimulation of active movement, and periods of immobilization should be minimized. Conclusions: SMA, DM, DMD and amyoplasia are heterogeneous conditions with a wide spectrum of muscle involvement. This investigation of muscle strength and motor function increases our knowledge concerning pattern and degree of muscle weakness in the different disorders, but also the impact of muscle weakness on motor function. The results have enhanced the possibilities of planning therapeutic interventions and the understanding of the prerequisites for everyday life in the children and adolescents with neuromuscular disorders

Legislative Documents

Also, variously referred to as: House bills; House documents; House legislative documents; legislative documents; General Court documents

The Education Act : Conditions for a Research-based School A Frame-Factor Theoretical Thinking

In 2010, the Swedish Parliament enacted a new education act that, among other aspects, stipulated education in primary and secondary schools must be based on research and proven experience. Such a legal requirement that would apply to both school levels is quite innovative not only in Sweden but internationally. Over the years principals and teachers have developed new pedagogies designed to improve teaching and learning. Could another means toward such improvements lie in a law stipulating that education in primary and secondary school must be based on research and proven experience? What conditions are required for such a law to affect the work of the school faculty and staff? The analytic methods used in this investigation are Lundgren’s frame factor theory and Goffman’s frame analysis. The focus is on the relationship between parliamentary control via legislation and the possibilities of principals and teachers to fulfil the intentions of the law. Our analysis reveals that the law experienced difficulties due to it not being properly implemented and not providing clear instructions on how it should be used in teaching practice