Gait analysis for individually tailored interdisciplinary interventions in children with cerebral palsy: a randomized controlled trial.

AIM: To test the hypothesis that improvements in gait and function following individualized interdisciplinary interventions consisting of physical therapy, orthotics, spasticity management, and orthopaedic surgery using instrumented gait analysis are superior to 'usual care' in children with cerebral palsy (CP). METHOD: This was a prospective, single-blind, parallel-group, randomized controlled trial investigating the effectiveness of interventions based on the use of gait analysis. Primary outcome was gait (Gait Deviation Index) and secondary outcomes were walking and patient-reported outcome measures of function, disability, and health-related quality of life. Follow-ups were done at 26 weeks (questionnaires) and at the primary end point of 52 weeks (all outcomes). RESULTS: Sixty participants with CP (39 males, 21 females, mean age 6y 10mo, standard deviation 1y 3mo, range 5y-9y 1mo) in Gross Motor Function Classification System levels I or II, were randomized to interventions with or without gait analysis. No significant or clinically relevant between-group differences in change scores of the primary or secondary outcomes were found. The recommended categories of interventions were dominated by non-surgical interventions and were applied in 36% to 86% of the participants. INTERPRETATION: Interventions using gait analysis were not superior to 'usual care' on gait, walking, or patient-reported outcomes in a sample of relatively young and independently walking children with CP not expected to need surgery. WHAT THIS PAPER ADDS: Gait analysis in children with cerebral palsy in Gross Motor Function Classification System levels I or II recommends interdisciplinary interventions. Compliance to interventions recommended after gait analysis was low. No statistically significant advantages were identified for the intervention group versus the control group.

ANÁLISIS DE MARCHA PARA LA INTERVENCIÓN INTERDISCIPLINARIA ADAPTADA INDIVIDUALMENTE EN NIÑOS CON PARÁLISIS CEREBRAL: ENSAYO CONTROLADO RANDOMIZADO: OBJETIVO: Comprobar la hipótesis que las mejoras en la marcha y la función luego de las intervenciones interdisciplinarias individualizadas de terapia física, ortésis, tratamiento antiespástico, y cirugía ortopédica son superiores que "tratamiento convencional" en parálisis cerebral (PC) utilizando un análisis de marcha instrumentada METODO: Este fue un ensayo randomizado controlado, prospectivo, ciego, con grupo paralelo que investigó la efectividad de intervenciones basada en el uso de análisis de marcha. El resultado primario fue la marcha (Índice de Desviación de la Marcha) y los resultados secundarios fueron el paso y los resultados reportados por los pacientes de función, discapacidad y calidad de vida relacionada a la salud. Los seguimientos se realizaron a las 26 semanas (cuestionarios) y el punto de fin primario de 52 semanas (todos los resultados). RESULTADOS: Sesenta participantes con PC (39 masculinos, 21 femeninos, edad media de 6 años 10 meses, desviación estándar de 1 años y 3 meses, rango 5 años 0 meses- 9 años y 1 mes) con niveles de GMFCS I o II, fueron asignados al azar intervenciones con y sin análisis de marcha. No se encontraron diferencias significativas o clínicamente relevantes entre los grupos en cuanto a los cambios de los resultados primarios y secundarios. INTERPRETACION: Las intervenciones que usaron análisis de marcha no fueron superiores al tratamiento convencional sobre el paso, la marcha o resultados reportados por los pacientes en una muestra de niños con PC relativamente jóvenes y de marcha independiente que no se espera que necesiten cirugía.

ANÁLISE DE MARCHA PARA INTERVENÇÕES INDIVIDUALMENTE PLANEJADAS EM CRIANÇAS COM PARALISIA CEREBRAL: UM ENSAIO CONTROLADO RANDOMIZADO: OBJETIVO: Testar a hipótese de que melhoras na marcha e função após intervenções interdisciplinares individualizadas consistindo de fisioterapia, órteses, manejo da espasticidade, e cirurgia ortopédica usando análise de marcha instrumentalizada são superiors comparadas ao "cuidado usual" em crianças com paralisia cerebral (PC). MÉTODO: Este foi um estudo randomizado controlado prospectivo, único cego, com grupos paralelos, investigando a efetividade de intervenções baseadas no uso da análise de marcha. O desfecho primário foi a marcha (Índice de Desvio da Marcha) e os desfechos secundários foram o caminhar e medidas relatadas pelo paciente da função, incapacidade, e qualidade de vida relacionada à saúde. Acompanhamentos foram feitos com 26 semanas (questionários) e o encerramento primário foi 52 semanas (todos os resultados). RESULTADOS: Sessenta participantes com PC (39 do sexo masculino, 21 do sexo feminino, média de idade 6a 10 m, desvio padrão 1a 3 m, variação 5a 0 m- 9a 1 m) nos níveis do Sistema de Classificação da Função Motora Grossa (GMFCS) I ou II foram fandomizados para intervenções com ou sem análise de marcha. Nenhuma diferença significativa ou clinicamente relevante entre grupos nos escores de mudança dos desfechos primários e secundários foram encontradas. As categorias de intervenção recomendadas foram dominadas pelas intervenções não-cirúrgicas e foram aplicadas em 36% a 86% dos participantes. INTERPRETAÇÃO: Intervenções usando análise de marcha não foram superiores ao "cuidado usual" para a marcha, o caminhar, ou resultados reportados por pacientes em ma amostra de crianças com PC relativamente jovens e com deambulação indepente, para a qual não se espera a necessidade de cirurgia.

A Faroese founder variant in TBCD causes early onset, progressive encephalopathy with a homogenous clinical course.

An intact and dynamic microtubule cytoskeleton is crucial for the development, differentiation, and maintenance of the mammalian cortex. Variants in a host of structural microtubulin-associated proteins have been identified to cause a wide spectrum of malformations of cortical development and alterations of microtubule dynamics have been recognized to cause or contribute to progressive neurodegenerative disorders. TBCD is one of the five tubulin-specific chaperones and is required for reversible assembly of the α-/ß-tubulin heterodimer. Recently, variants in TBCD, and one other tubulin-specific chaperone, TBCE, have been identified in patients with distinct progressive encephalopathy with a seemingly broad clinical spectrum. Here, we report the clinical, neuroradiological, and neuropathological features in eight patients originating from the Faroe Islands, who presented with an early onset, progressive encephalopathy with features of primary neurodegeneration, and a homogenous clinical course. These patients were homozygous for a TBCD missense variant c.[3099C>G]; p.(Asn1033Lys), which we show has a high carrier frequency in the Faroese population (2.6%). The patients had similar age of onset as the previously reported patients (n = 24), but much shorter survival, which could be caused by either differences in supportive treatment, or alternatively, that shorter survival is intrinsic to the Faroese phenotype. We present a detailed description of the neuropathology and MR imaging characteristics of a subset of these patients, adding insight into the phenotype of TBCD-related encephalopathy. The finding of a Faroese founder variant will allow targeted genetic diagnostics in patients of Faroese descent as well as improved genetic counseling and testing of at-risk couples.

17q12 deletion and duplication syndrome in Denmark-A clinical cohort of 38 patients and review of the literature.

17q12 deletions and duplications are two distinct, recurrent chromosomal aberrations usually diagnosed by chromosomal microarray analysis (CMA). The aberrations encompass the genes, HNF1B, LHX1, and ACACA, among others. We here describe a large national cohort of 12 phenotyped patients with 17q12 deletions and 26 phenotyped patients with 17q12 duplications. The total cohort includes 19 index patients and 19 family members. We also reviewed the literature in order to further improve the basis for the counseling. We emphasize that renal disease, learning disability, behavioral abnormalities, epilepsy, autism, schizophrenia, structural brain abnormalities, facial dysmorphism, and joint laxity are features seen in both the 17q12 deletion syndrome and the reciprocal 17q12 duplication syndrome; and we extend the list of features seen in both patient categories to include strabismus, esophageal defects, and duodenal atresia. Delayed language development, learning disability, kidney involvement, and eye dysmorphism and strabismus were the most consistently shared features among patients with 17q12 deletion. Patients with 17q12 duplications were characterized by an extremely wide phenotypic spectrum, including a variable degree of learning disabilities, delayed language development, delayed motor milestones, and a broad range of psychiatric and neurological features. This patient group also included adults achieving an academic degree. Assessing index patients and non-index patients separately, our observations illustrate that an overall milder disease burden is seen, in particular in patients with 17q12 duplications who are ascertained on the duplication rather than the phenotype. This evidence may be useful in prenatal counseling. © 2016 Wiley Periodicals, Inc.

The use of instrumented gait analysis for individually tailored interdisciplinary interventions in children with cerebral palsy: a randomised controlled trial protocol.

BACKGROUND: Children with cerebral palsy (CP) often have an altered gait. Orthopaedic surgery, spasticity management, physical therapy and orthotics are used to improve the gait. Interventions are individually tailored and are planned on the basis of clinical examinations and standardised measurements to assess walking ('care as usual'). However, these measurements do not describe features in the gait that reflect underlying neuro-musculoskeletal impairments. This can be done with 3-dimensional instrumented gait analysis (IGA). The aim of this study is to test the hypothesis that improvements in gait following individually tailored interventions when IGA is used are superior to those following 'care as usual'. METHODS/DESIGN: A prospective, single blind, randomised, parallel group study will be conducted. Children aged 5 to 8 years with spastic CP, classified at Gross Motor Function Classification System levels I or II, will be included. The interventions under investigation are: 1) individually tailored interdisciplinary interventions based on the use of IGA, and 2) 'care as usual'. The primary outcome is gait measured by the Gait Deviation Index. Secondary outcome measures are: walking performance (1-min walk test) and patient-reported outcomes of functional mobility (Pediatric Evaluation of Disability Inventory), health-related quality of life (The Pediatric Quality of Life Inventory Cerebral Palsy Module) and overall health, pain and participation (The Pediatric Outcome Data Collection Instrument). The primary endpoint for assessing the outcome of the two interventions will be 52 weeks after start of intervention. A follow up will also be performed at 26 weeks; however, exclusively for the patient-reported outcomes. DISCUSSION: To our knowledge, this is the first randomised controlled trial comparing the effects of an individually tailored interdisciplinary intervention based on the use of IGA versus 'care as usual' in children with CP. Consequently, the study will provide novel evidence for the use of IGA. TRIAL REGISTRATION: ClinicalTrials.gov NCT02160457 . Registered June 2, 2014.