Brain MRI Abnormalities, Epilepsy and Intellectual Disability in LAMA2 Related Dystrophy - a Genotype/Phenotype Correlation.

BACKGROUND: LAMA2-related muscular dystrophy is a disorder that causes muscle weakness and varies in severity, from a severe, congenital type to a milder, late-onset form. However, the disease does not only affect the muscles, but has systemic involvement and can lead to alterations such as brain malformation, epilepsy and intellectual disability. OBJECTIVE: Describe the frequency of cortical malformations, epilepsy and intellectual disability in LAMA2-RD in a Brazilian cohort and correlate the neurological findings to genetic and motor function. METHODS: This is an observational study of 52 LAMA2-RD patients, who were divided into motor function subgroups and compared based on brain MRI findings, epilepsy, intellectual disability, and type of variants and variant domains. RESULTS: 44 patients (84.6%) were only able to sit, and 8 patients (15.4%) were able to walk. 10 patients (19.2%) presented with cortical malformations (polymicrogyria, lissencephaly-pachygyria, and cobblestone),10 patients (19.2%) presented with epilepsy, and 8 (15.4%) had intellectual disability. CNS manifestations correlated with a more severe motor phenotype and none of the patients able to walk presented with cortical malformation or epilepsy. There was a relation between gene variants affecting the laminin-α2 LG-domain and the presence of brain malformation (P = 0.016). There was also a relation between the presence of null variants and central nervous system involvement. A new brazilian possible founder variant was found in 11 patients (21,15%) (c.1255del; p. Ile419Leufs*4). CONCLUSION: Cortical malformations, epilepsy and intellectual disability are more frequent among LAMA2-RD patients than previously reported and correlate with motor function severity and the presence of variants affecting the laminin-α2 LG domain. This brings more insight fore phenotype-genotype correlations, shows the importance of reviewing the brain MRI of patients with LAMA2-RD and allows greater attention to the risk of brain malformation, epilepsy, and intellectual disability in those patients with variants that affect the LG domain.

Hypoglycemia in Patients With LAMA2-CMD.

BACKGROUND: Hypoglycemia has been reported in patients with LAMA2-CMD, but the frequency, risk factors, and correlation to genotype/phenotype have not been systematically assessed to date. METHODS: A retrospective cohort study was performed on 48 patients with LAMA2-CMD. Patients were divided into two groups: a hypoglycemic group, with at least one episode of hypoglycemia, and a nonhypoglycemic group. The groups were compared according to gait function, epilepsy, intellectual disability, constipation, gastroesophageal reflux, gastrostomy, weight percentile, scoliosis, the use of a ventilator device, the use of a feeding device, neuromuscular disease swallowing status scale, and type of mutation. RESULTS: Fifteen patients (31.2%) presented with at least one episode of symptomatic hypoglycemia and eight (16.6% of the cohort) had two or more episodes. All patients who had hypoglycemia were in the nonambulant group. We observed a correlation between gait, the use of ventilator and feeding devices, and swallow function with hypoglycemia. Patients with extremely low weight were five times more likely to have recurrent episodes of hypoglycemia. The presence of at least one missense variant appears to be associated with a lower risk of hypoglycemia. CONCLUSION: Patients with LAMA2-CMD are at risk of hypoglycemia. The risk is more relevant in patients with severe phenotype and patients with loss-of-function variants. For patients with extremely low weight, the risk is higher. Blood glucose should be actively measured in patients who are fasting or have infections, and health care providers should be prepared to identify and treat these patients.

Clinical Manifestation of Nebulin-Associated Nemaline Myopathy.

Background and Objectives: Nemaline myopathy (NM) is a genetically heterogeneous inherited myopathy related with at least 12 genes, whereas pathogenic variants in NEB gene are the most common genetic cause. The clinical spectrum of NM caused by NEB pathogenic variants (NM-NEB) is very broad, ranging from mild to severe presentations manifesting with generalized weakness, as well as respiratory and bulbar involvement. There is currently not enough data regarding the progression of the disease. In this study, we present a genotypic and phenotypic spectrum of 33 patients with NM caused by NEB variants (NM-NEB) classified according to age groups and the use of ventilatory support. We focused on interventional support, genotype-phenotype correlation, and association between respiratory, bulbar, and motor systems in groups of patients stratified by age and by the use of ventilatory support (VS). Methods: Clinical and genetic data from patients with NM-NEB followed up in one specialized center were collected through regular consultations. Patients were evaluated regarding motor, bulbar, and respiratory functions. Results: Thirty-three patients with NM-NEB were evaluated consisting of 15 females and 18 males with an average age of 18 (±12) years and a median of 17 (±11) years. 32% of patients with NM-NEB used a G tube, 35% were not able to walk without support, and 55% needed VS. Scoliosis and dysphagia were more common among patients who used VS. Described for the first time, half of the patients presented tongue atrophy in a triple furrow pattern, and the presence of the atrophy was associated with dysphagia. Comparing the patients grouped by age, we found that, proportionally, older patients had more scoliosis and respiratory dysfunction than younger groups, suggesting the progression of the disease in these domains. In addition to that, we showed that VS use was associated with scoliosis and dysphagia. Discussion: NM-NEB is a very debilitating disease. There is an association between scoliosis and respiratory dysfunction while patients using VS have more often scoliosis than the no-VS group. Triple furrow tongue atrophy is a novel and frequent finding, which is directly associated with dysphagia. Grouping patients by age suggested disease stability in motor and swallow function, but a progression in respiratory dysfunction and skeletal deformities. All observations are relevant in the management care of patients with NM.

Motor Compensation Strategies for Reduced Upper Limb Function Among Individuals With Duchenne Muscular Dystrophy.

The purpose of this longitudinal study was to identify and verify the compensatory motor strategies for upper limb functioning of individuals with Duchenne Muscular Dystrophy (DMD). We evaluated 32 patients diagnosed with DMD (aged 6-19 years) for cognitive and motor functioning using the Mini Mental State Examination (MMSE), Vignos Scale Jebsen Taylor Test (JTT) and Functional Skill Scale (FSS) at baseline testing and over retest intervals of six and 12 months. We used the MMSE to screen participants for capacity to engage in the research, and we analyzed absolute and percentile changes in the frequency distribution of motor strategies participants used on each JTT subtest. We also used analysis of variance with repeated measures and Bonferroni post-hoc testing of multiple comparisons to identify disease progression through FSS scores. We observed an increased frequency of compensatory motor strategies over six months. We recommend the associated use of the JTT and FSS to assess patients with DMD, since we observed worsened movement quality over a time interval of six months even while essential motor competence was maintained.

Interactive Video Gaming Improves Functional Balance in Poststroke Individuals: Meta-Analysis of Randomized Controlled Trials.

The main objective of this study was to evaluate the effects of interactive video games on functional balance and mobility in poststroke individuals. The Health Science databases accessed included Medline via PubMed, LILACS, SciELO, and PEDro. The inclusion criteria were as follows: clinical studies evaluating the use of interactive video games as a treatment to improve functional balance and mobility in individuals poststroke and studies published in the Brazilian Portuguese, English, or Spanish language between 2005 and April 2016. PEDro Scale was used to analyze the methodological quality of the studies. The Berg Balance Scale and Timed Up and Go Test (TUGT) data were evaluated using a meta-analysis, the publication bias was assessed by funnel plots, and the heterogeneity of the studies by I2 statistic. Eleven studies were included in the final analysis. Functional balance improved in individuals treated using interactive video games (mean difference = 2.24, 95% confidence interval [0.45, 4.04], p = .01), but no improvement was observed in mobility as measured by TUGT. The studies presented low heterogeneity (24%). The mean score on the PEDro Scale was 6.2 ± 1.9. Interactive video games were effective in improving functional balance but did not influence the mobility of individuals poststroke.

Independência funcional de crianças de um a quatro anos com mielomeningocele / Independencia funcional de niños de un a cuatro años con mielomeningocele / Functional independence of one- to four-year-old children with myelomeningocele

RESUMO A mielomeningocele é causada por defeito no fechamento do tubo neural. A doença representa a segunda causa de deficiência crônica no aparelho locomotor em crianças. A independência funcional depende do nível da lesão medular e sua avaliação é importante para a determinação de abordagens terapêuticas adequadas. O objetivo foi descrever a independência funcional e o nível de lesão de 15 crianças de seis meses a quatro anos com lesão medular completa causada por mielomeningocele. Foi realizado um estudo observacional do tipo transversal nas Universidades Ibirapuera e Santa Cecília. O Inventário de Avaliação Pediátrica de Incapacidade (Pediatric Evaluation of Disability Inventory - PEDI) foi aplicado com os pais, para avaliação da independência funcional nas atividades de vida diária das crianças. A escala de Padrões Internacionais para Classificação Neurológica de Lesão da Medula Espinhal da Associação Americana de Lesão Medular (International Standards for Neurological Classification of Spinal Cord Injury of the American Spinal Injury Association) foi utilizada para determinar o nível motor e sensitivo da lesão. Foram avaliados seis meninos e nove meninas (27,0±11,8 meses de idade). Três crianças apresentaram lesão torácica, nove apresentaram lesão lombar alta, duas apresentaram lesão lombar baixa e uma apresentou lesão sacral. As pontuações na PEDI variaram de 15 a 60% no domínio autocuidado, de 10 a 15% no domínio mobilidade e de 19 a 58% no domínio função social. Houve grande variabilidade no desempenho funcional de crianças com mielomeningocele, detectada pelos domínios autocuidado e função social da PEDI. As crianças apresentaram grande prejuízo no domínio mobilidade.

RESUMEN El mielomeningocele es causado por defecto en el cierre del tubo neural. La enfermedad representa la segunda causa de deficiencia crónica en el aparato locomotor en niños. La independencia funcional depende del nivel de la lesión medular y su evaluación es importante para determinar enfoques terapéuticos adecuados. El objetivo fue describir la independencia funcional y el nivel de lesión de 15 niños de seis meses a cuatro años con lesión medular completa causada por mielomeningocele. Se realizó un estudio observacional del tipo transversal en las Universidades Ibirapuera y Santa Cecilia. Se aplicó el Inventario de Evaluación Pediátrica de Discapacidad (Pediatric Evaluation of Disability Inventory, PEDI) con los padres para evaluar la independencia funcional en las actividades de vida diaria de los niños. La escala de Estándares Internacionales para la Clasificación Neurológica de la Lesión Medular de la Asociación Americana de la Lesión Medular (International Standards for Neurological Classification of Spinal Cord Injury of the American Spinal Injury Association) fue utilizada para determinar el nivel motor y sensitivo de la lesión. Se evaluaron seis niños y nueve niñas (27,0 ± 11,8 meses de edad). Tres niños presentaron lesión torácica, nueve presentaron lesión lumbar alta, dos presentaron lesión lumbar baja y una presentó lesión en el sacro. Las puntuaciones en la PEDI variaron del 15 al 60% en el dominio autocuidado, del 10 al 15% en el ámbito de la movilidad y del 19 al 58% en el ámbito de la función social. Hubo gran variabilidad en el desempeño funcional de los niños con mielomeningocele, detectada por los campos autocuidado y función social de la PEDI. Los niños presentaron gran daño en el dominio de la movilidad.

ABSTRACT Myelomeningocele is caused by neural tube closure defects and represents the second cause of locomotion disability in children. Functional independence depends on level of spine injury and assessment is important to determine proper therapeutic approaches. We aimed to describe functional Independence and level of injury in 15 children, aged one to four years and with complete spinal cord injury caused by myelomeningocele. This is an observational transversal study developed in the Ibirapuera University and Santa Cecília University. The Pediatric Evaluation of Disability Inventory (PEDI) was used to ask parents about the functional independence of children in daily life activities. The International Standards for Neurological Classification of Spinal Cord Injury of the American Spinal Injury Association was used to determine the motor and sensory levels. Nine girls and six boys were assessed (27.0 ±11.8 months of age). Three children showed thoracic level, nine showed high lumbar level, two were classified as low lumbar, and one as sacral level. PEDI scores varied from 15 to 60% on the self-care area, from 10 to 15% on mobility, and from 19 to 58% on social function. High variability was observed on the functional independence of children with myelomeningocele, detected by self-care and social function areas of PEDI. Mobility was the most affected domain.

Reliability, validity and description of timed performance of the Jebsen-Taylor Test in patients with muscular dystrophies.

BACKGROUND: The Jebsen-Taylor Test evaluates upper limb function by measuring timed performance on everyday activities. The test is used to assess and monitor the progression of patients with Parkinson disease, cerebral palsy, stroke and brain injury. OBJECTIVES: To analyze the reliability, internal consistency and validity of the Jebsen-Taylor Test in people with Muscular Dystrophy and to describe and classify upper limb timed performance of people with Muscular Dystrophy. METHODS: Fifty patients with Muscular Dystrophy were assessed. Non-dominant and dominant upper limb performances on the Jebsen-Taylor Test were filmed. Two raters evaluated timed performance for inter-rater reliability analysis. Test-retest reliability was investigated by using intraclass correlation coefficients. Internal consistency was assessed using the Cronbach alpha. Construct validity was conducted by comparing the Jebsen-Taylor Test with the Performance of Upper Limb. RESULTS: The internal consistency of Jebsen-Taylor Test was good (Cronbach's α=0.98). A very high inter-rater reliability (0.903-0.999), except for writing with an Intraclass correlation coefficient of 0.772-1.000. Strong correlations between the Jebsen-Taylor Test and the Performance of Upper Limb Module were found (rho=-0.712). CONCLUSION: The Jebsen-Taylor Test is a reliable and valid measure of timed performance for people with Muscular Dystrophy.

Correlation between temporal-spatial parameters and manual ability of adults with dyskinetic cerebral palsy / Correlación entre los parámetros espacio-temporales y la habilidad manual de adultos con parálisis cerebral tipo discinética / Correlação entre os parâmetros espaçotemporais e a habilidade manual de adultos com paralisia cerebral do tipo discinético

The aim of this study was to verify relation between kinematic variables of temporal-spatial parameters and manual ability and between own temporal-spatial variables during the movement of bring a mug to the mouth in adults with dyskinetic cerebral palsy (DCP). Sixteen adults with DCP were evaluated by MACS (Manual Ability Classification System), and by temporal-spatial variables of tridimensional kinematics of the movement to bring a bug to the mouth by means of 9 cameras infra-red Vicon(r) MX 40 (Oxford Metrics Group, Oxford, UK). The Spearman correlation coefficient (ρ) was used to correlate variables. As a result, we found weak correlation between the classification of manual ability and the adjusting phase (ρ=0.219), the velocity variables - average velocity (ρ=-0.313), peak velocity (ρ=-0.282) and time to peak velocity (ρ=-0.250). No correlation was found between the variables going and returning phase and MACS. Moderate correlation was found between going and returning phase (ρ=0.559), between the going phase and time to peak velocity (ρ=0.518) and between the adjusting phase and peak velocity (ρ=-0.562). A strong correlation was found between the mean velocity and peak velocity (ρ=0.947) and between the adjusting phase and average velocity (ρ=-0.635). In conclusion, functional impairment may be related to longer adjusting phase and decrease of movement speed in subjects with PCD. Kinematic variables were related to each other in moderate and strong way and indicated that the phases runtime influences the movement speed.

El objetivo de este estudio fue verificar si hay una relación entre las variables cinemáticas espacio-temporales y la habilidad manual y entre las propias variables espacio-temporales estudiadas durante el movimiento de traer una taza a la boca en adultos con parálisis cerebral tipo discinética (PCD). Dieciséis adultos con PCD fueron sometidos a una evaluación de habilidad manual por medio de la escala MACS (Manual Ability Classification System) y análisis de las variables espacio-temporales de la cinemática tridimensional del movimiento para llevar una taza a la boca por medio de 9 cámaras infrarrojas Vicon(r) MX 40 (Oxford Metrics Group, Oxford, UK). El coeficiente de correlación de Spearman (r) fue aplicado para verificar la relación entre las variables estudiadas. Como resultado, fue encontrada una débil correlación entre la clasificación de la habilidad manual y la fase de ajuste del movimiento (r=0,219), las variables de velocidad - velocidad media (r=-0,313), velocidad máxima (r=-0,282) y tiempo para alcanzar la velocidad máxima (r=-0,250). No se encontró correlación entre la variable tiempo de ida y la variable de regreso del movimiento y la MACS. Correlación moderada se encontró entre la fase de ida y la fase de regreso del movimiento (r=0,559), entre la fase de ida y el tiempo para alcanzar la velocidad máxima (r=0,518) y entre la fase de ajuste y la velocidad máxima (r=-0,562). Fuerte correlación se encontró entre la velocidad media y la velocidad máxima (r=0,947) y entre la fase de ajuste y la velocidad media (r=-0,635). A modo de conclusión, el perjuicio funcional puede ser relacionado con más tiempo de ejecución de la fase de ajuste y con la reducción de la velocidad del movimiento en sujetos con PCD. Las variables cinemáticas se relacionaban de manera moderada y fuerte e.

O objetivo deste estudo foi verificar se existe relação entre as variáveis cinemáticas espaçotemporais e a habilidade manual e entre as próprias variáveis espaçotemporais estudadas durante o movimento de levar uma caneca à boca em indivíduos adultos com paralisia cerebral do tipo discinético (PCD). Dezesseis adultos com PCD foram submetidos à avaliação da habilidade manual por meio da escala MACS (Manual Ability Classification System) e análise das variáveis espaçotemporais da cinemática tridimensional do movimento de levar uma caneca à boca por meio de 9 câmeras de infravermelho Vicon(r) MX 40 (Oxford Metrics Group, Oxford, UK). O coeficiente de correlação de Spearman (ρ) foi aplicado para verificar relação entre as variáveis estudadas. Como resultado, foi encontrada fraca correlação entre a classificação da habilidade manual e a fase de ajuste do movimento (ρ=0,219), as variáveis de velocidade - velocidade média (ρ=-0,313), velocidade máxima (ρ=-0,282) e tempo para atingir o pico de velocidade (ρ=-0,250). Não foi encontrada correlação entre a variável tempo de ida e a variável tempo de retorno do movimento e a MACS. Correlação moderada foi encontrada entre a fase de ida e a fase de retorno do movimento (ρ=0,559), entre a fase de ida e o tempo para atingir o pico de velocidade (ρ=0,518) e entre a fase de ajuste e a velocidade máxima (ρ=-0,562). Forte correlação foi encontrada entre a velocidade média e o pico de velocidade (ρ=0,947) e entre a fase de ajuste e a velocidade média (ρ=-0,635). Como conclusão, o prejuízo funcional pode ser relacionado ao maior tempo de execução da fase de ajuste e com a redução da velocidade do movimento em indivíduos com PCD. As variáveis cinemáticas se relacionaram de maneira moderada e forte e indicaram que o tempo de execução das fases influencia a velocidade do movimento.

Three-dimensional analysis of performance of an upper limb functional task among adults with dyskinetic cerebral palsy.

Patients with dyskinetic cerebral palsy (DCP) experience considerable variability in their purposeful movements due to involuntary movements that contribute to functional impairment. Movement analyses can demonstrate how the movements involved in bringing a mug to the mouth are performed by patients with DCP. Sixteen adults with DCP (29.63±4.42 years) and eleven healthy adults (24.09±3.73 years) performed six consecutive movements of bringing a mug to the mouth using their dominant arm. The mug was placed at 75% of each subject's maximum reach. Kinematic data were captured by 10 cameras and processed using biomechanical software. Fifteen reflexive markers were placed on predetermined bony landmarks on the head, trunk and upper limbs. DCP adults required more time to perform the going (bringing the mug to the mouth), adjusting (simulating taking a drink) and returning (lowering the mug back to the table) phases, and their movements were less smooth than the controls, as indicated by the index of curvature, average jerk and number of movement units. The DCP adults took a longer time to complete the task than controls as indicated by the peak velocities, mean velocities and times to peak velocity. With respect to the angular parameters, DCP adults had a smaller range of motion for shoulder and elbow flexion and forearm pronation compared with the controls. The analysis of functional tasks represents an important measure for the evaluation of dyskinetic movements and permits the quantitative characterization of upper limb impairment in adults with DCP.