Functional mobility in children and young adults with Dravet syndrome.

AIM: This cohort study aimed to describe functional mobility in Dravet syndrome, a developmental and epileptic encephalopathy. METHOD: Functional mobility was assessed in individuals (aged 3-25 years), diagnosed with Dravet syndrome, using the Functional Mobility Scale (FMS), Mobility Questionnaire 28 (MobQues28), and estimated walking distance. Secondary outcome variables were Gait Profile Score (GPS), walking velocity, age at independent walking, intellectual disability, seizure frequency, genetic variant type, and body mass index (BMI). RESULTS: Forty participants aged 3 years to 24 years 2 months (mean = 12 years 2 months) had a median MobQues28 of 79%, median scores of 5, 5, and 4 for the FMS 5 m, 50 m, and 500 m and a median estimated walking distance of 1 km to 3 km. Most difficulties were seen in walking up and down the stairs, walking over obstacles, kicking a ball, and running. MobQues28 scores showed a significant decrease (-6.6%, p = 0.016) in the age category of young adults (≥18 years). After correcting for age, MobQues28 was correlated to age at independent walking (-0.485, p = 0.002), GPS (-0.460, p = 0.003), and walking velocity (0.334, p = 0.038). Analysis of variance showed a significant effect of intellectual disability and BMI on MobQues28 (p = 0.029, p = 0.049). No effect of seizure frequency or genetic variant was found (p = 0.579, p = 0.337). INTERPRETATION: Functional mobility limitations were observed mainly in dual tasks and activities requiring stability, with limitations increasing from the age of 18 years. Age at independent walking, gait impairments, intellectual disability, and BMI can impact functional mobility in Dravet syndrome. WHAT THIS PAPER ADDS: Most limitations were seen in dual task activities and activities that required more stability. Deterioration in functional mobility occurred in young adults. The more gait impairments, the more functional mobility limitations. Age at independent walking, intellectual disability, and body mass index can impact functional mobility.

Strength measurements in patients with Dravet Syndrome.

BACKGROUND: Dravet Syndrome (DS) is a developmental and epileptic encephalopathy, characterized by drug resistant infantile onset seizures and cognitive and motor impairment. Walking problems progressively occur and crouch gait is frequently observed. Muscle weakness is hypothesized as contributing impairment. Yet, so far, no studies have performed strength measurements in patients with DS, most likely due to cognitive impairment. AIMS: To determine the feasibility and validity of strength measurements in the framework of gait analysis and to outline strength problems in patients with DS. METHODS: Manual muscle testing, dynamometry (hand grip strength and handheld dynamometry) and functional tests (underarm throwing, standing long jump, sit-to-stand, stair climbing) were performed in 46 patients with DS. Results were compared to age-related reference values from literature. RESULTS: Forty one percent (19/46) of the patients (aged 5.2-24.8 years, median: 15.8 years) accomplished all measurements and scored generally below the fifth percentile of norm values. The remaining 59% (27/46) was not able to complete all strength assessment due to cognitive, behavioural and motor difficulties. Handheld dynamometry seemed most sensitive and specific to detect isolated muscle strength. Validity of the functional tests was controversial, as motor proficiency, balance and coordination may interfere. CONCLUSION: Although measuring strength in patients with DS was challenging in the context of gait analysis, decreased muscle strength was observed in patients that could perform strength measurements. Handheld dynamometry is preferred over functional tests for future investigations of muscle strength and its interference with gait are required for better understanding of walking problems.

Deconstructing Dravet syndrome neurocognitive development: A scoping review.

Dravet syndrome (DS) is a rare severe epilepsy syndrome associated with slowed psychomotor development and behavioral disorders from the second year onward in a previously seemingly normal child. Among cognitive impairments, visuospatial, sensorimotor integration, and expressive language deficits are consistently reported. There have been independent hypotheses to deconstruct the typical cognitive development in DS (dorsal stream vulnerability, cerebellar-like pattern, sensorimotor integration deficit), but an encompassing framework is still lacking. We performed a scoping review of existing evidence to map the current understanding of DS cognitive and behavioral developmental profiles and to summarize the evidence on suggested frameworks. We searched PubMed, Scopus, PsycInfo, and MEDLINE to identify reports focusing on cognitive deficits and/or behavioral abnormalities in DS published between 1978 and March 15, 2020. We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Twenty-one reports were selected and tabulated by three independent reviewers based on predefined data extraction and eligibility forms. Eighteen reports provided assessments of global intelligence quotients with variable degrees of cognitive impairment. Eleven reports analyzed single subitems contribution to global cognitive scores: these reports showed consistently larger impairment in performance scales compared to verbal ones. Studies assessing specific cognitive functions demonstrated deterioration of early visual processing, fine and gross motor abilities, visuomotor and auditory-motor integration, spatial processing, visuo-attentive abilities, executive functions, and expressive language. Behavioral abnormalities, reported from 14 studies, highlighted autistic-like traits and attention and hyperactivity disorders, slightly improving with age. The cognitive profile in DS and some behavioral and motor abnormalities may be enclosed within a unified theoretical framework of the three main hypotheses advanced: a pervasive sensorimotor integration deficit, encompassing an occipito-parietofrontal circuit (dorsal stream) dysfunction and a coexistent cerebellar deficit.

The mechanics behind gait problems in patients with Dravet Syndrome.

BACKGROUND: Dravet Syndrome (DS) is a developmental and epileptic encephalopathy starting in infancy and characterised by treatment resistant epilepsy with cognitive impairment and progressive motor dysfunction. Walking becomes markedly impaired with age, but the mechanical nature of gait problems remains unclear. RESEARCH QUESTION: What are the kinetic strategies characterised in gait of patients with DS? METHODS: This case-control study compared 41 patients with DS aged 5.2-26.1 years (19 female, 22 male) to 41 typically developing (TD) peers. Three dimensional gait analysis (VICON) was performed to obtain spatiotemporal parameters, kinematics and kinetics during barefoot, level walking at self-selected walking velocity. The sagittal plane support moment was analysed using Statistical Parametric Mapping (SPM). Three DS subgroups were identified based on differences in kinetic strategies characterised by the net internal knee joint moments and trunk lean. Kinematic and kinetic time profiles of the subgroups were compared to the TD group (SPM t-test). Clinical characteristics from physical examination and parental anamnesis were compared between DS (sub)groups using non-parametric tests (Kruskal-Wallis, Wilcoxon rank-sum, Fisher's exact). RESULTS: Support moments in stance were significantly increased in the DS group compared to TD and strongly related to minimum knee flexion in midstance. Persistent internal knee extension moments during stance were detected in a subgroup of 27 % of the patients. A second subgroup of 34 % showed forward trunk lean and attained internal knee flexion moments. The remaining 39 % had neutral or backward trunk lean with internal knee flexion moments. Subgroups differed significantly in age and functional mobility. SIGNIFICANCE: Inefficient kinetic patterns suggested that increased muscle effort was needed to control lower limb stability. Three distinct kinetic strategies that underly kinematic deviations were identified. Clinical evaluation of gait should pay attention to knee angles, trunk lean and support moments.

Independent walking and cognitive development in preschool children with Dravet syndrome.

AIM: To investigate the relation between cognitive and motor development in preschool aged children with Dravet syndrome, in particular between the age of independent walking and cognitive development. METHOD: Results of cognitive and motor developmental assessments and the age of independent walking were retrieved retrospectively from the medical records of 33 children (17 males, 16 females; mean age at last evaluation 33.2mo, SD 8.2mo, range 9-48mo) diagnosed with Dravet syndrome. Cognitive and motor developmental age, derived from the Bayley Scales of Infant Development or through standardized neurodevelopmental assessment, were converted into cognitive and motor developmental quotients. Multiple test scores per child were included. RESULTS: A strong positive relation was found between cognitive and motor developmental quotient (Pearson r=0.854; p<0.001) in 20 children (slope=0.75; 95% CI: 0.54-0.95). A later age of independent walking was associated with a lower cognitive developmental quotient (28 children; p<0.001; slope=-1.01; 95% CI: -1.53 to -0.49). A higher cognitive developmental quotient was seen in children with an age at testing younger than 24 months. The cognitive developmental quotient of children with a delay in independent walking (>17.6mo) was significantly lower than those without a delay (p=0.006). INTERPRETATION: A strong relation exists between cognitive and motor development. Furthermore, the age of independent walking might be an important indicator of the development of children with Dravet syndrome. WHAT THIS PAPER ADDS: Cognitive and motor development are strongly related in children with Dravet syndrome. Later age of independent walking is associated with worse cognitive development in children with Dravet syndrome.

Gait deviations in patients with dravet syndrome: A systematic review.

BACKGROUND: Dravet Syndrome is a rare developmental and epileptic encephalopathy characterised by epileptic seizures, cognitive impairment and motor disorders. Gait is markedly impaired and could benefit from targeted intervention to improve quality of life for patient and caregivers. OBJECTIVE: To establish the state of the art regarding gait deviations in patients with Dravet Syndrome. METHODS: A systematic search was performed in Pubmed, Web of Science, Science Direct and Embase. Studies that assessed gait deviations in patients diagnosed with Dravet Syndrome using clinical observation, video gait analysis or three dimensional (3D) gait analysis and reported gait characteristics, spatiotemporal or kinematic outcomes were included. Screening, quality assessment and data extraction were performed by independent reviewers. RESULTS: Out of a total of 478 citations, nine articles were included. The total study population had an age range from 2.5 to 47 years. Three studies used clinical observation, three studies video analysis and three studies 3D gait analysis. Crouch gait was observed in about half of the population next to a variety of other gait deviations such as parkinsonian and cerebellar gait. Other findings included abnormalities in spatiotemporal parameters and kinematics, passive knee extension deficits, skeletal malalignment and neurological signs. CONCLUSIONS: A variety of gait characteristics was observed with crouch gait being the most reported gait pattern. Inconsistency in methods and findings from clinical and instrumented evaluation impede thorough understanding of the causal mechanism and evolution behind these deviations. PROSPERO REGISTRATION NUMBER: CRD42017070370.

Motor development in children with Dravet syndrome.

AIM: The aim of this study is to describe the course of motor development in children with Dravet syndrome. METHOD: Forty-three participants (21 males, 22 females; mean age at last assessment 53.89mo±42.50mo) met the inclusion criteria of having a confirmed diagnosis of Dravet syndrome and presence of data on motor development. All data between 1985 and 2018 were derived retrospectively from their medical records. Gross motor milestones and motor age equivalents were used to describe motor development. Standardized neurodevelopmental assessment and the Bayley Scales of Infant Development defined the overall motor development. Peabody Developmental Motor Scales, Bruininks-Oseretsky Test of Motor Proficiency, and the Beery-Buktenica Developmental Test of Visual-Motor Integration were used to describe development in specific motor domains. RESULTS: Children with Dravet syndrome showed a delay in both sitting (seven out of 14) and walking independently (11 out of 25). Overall motor age equivalents revealed a delay in 29 out of 38 assessments (age 9-115mo). All assessments of children older than 2 years (16 out of 16) showed a delay. Gross motor delay was present in seven out of seven and fine motor delay in 10 out of 13 assessments (age 19-167mo). INTERPRETATION: Motor development is delayed in the majority of children with Dravet syndrome older than 2 years and increases with age. WHAT THIS PAPER ADDS: A delay in motor development is present in most children with Dravet syndrome older than 2 years. Large diversity in early gross motor milestones confirms heterogeneity in Dravet syndrome.

Desarrollo motor en niños con el síndrome de Dravet OBJETIVO: El objetivo de este estudio es describir el curso del desarrollo motor en los niños con síndrome de Dravet. METODOLOGÍA: Cuarenta y tres participantes (21 niños, 22 niñas; con edad promedio en la última evaluación de 53,89 meses ± 42,50 meses) cumplieron los criterios de inclusión: tener un diagnóstico confirmado de síndrome de Dravet y presentar datos de desarrollo motor. Todos los datos recogidos entre 1,985 y 2,018 fueron extraídos retrospectivamente de las historias clínicas. Los hitos de motricidad gruesa y las equivalencias de edad motora se utilizaron para describir el desarrollo motor. Evaluaciones del neurodesarrollo estandarizadas y la escala de desarrollo infantil Bayley definieron el desarrollo motor global. La escala de desarrollo motor Peabody, el test de competencia motora Bruininks-Oseretsky y el test de desarrollo de la integración visomotora Beery-Buktenica se utilizaron para describir el desarrollo en los dominios motores específicos. RESULTADOS: Los niños con el síndrome de Dravet mostraron un retraso tanto en sentarse (7 de 14) como en caminar de manera independiente (11 de 25). En conjunto, las edades motoras equivalentes revelaron un retraso en 29 de las 38 evaluaciones (edad de 9-115 meses). Todas las evaluaciones de niños mayores de 2 años (16 de 16) mostraron un retraso. El retraso de la motricidad gruesa estuvo presente en 7 de 7 evaluaciones y el retraso de la motricidad fina en 10 de 13 evaluaciones (edad 19-167 meses). INTERPRETACIÓN: El desarrollo motor está retrasado en la mayoría de los niños con síndrome de Dravet mayores de dos años y aumenta con la edad.

Desenvolvimento motor em crianças com síndrome de Dravet OBJETIVO: O objetivo deste estudo é descrever o curso do desenvolvimento motor em crianças com síndrome de Dravet. MÉTODO: Quarenta e três participantes (21 do sexo masculino, 22 do sexo feminino; média de idade na última avaliação 53,89m ± 42,50m) atenderam aos critérios de inclusão de ter um diagnóstico confirmado de síndrome de Dravet e a presença de dados sobre o desenvolvimento motor. Todos os dados entre 1985 e 2018 foram derivados retrospectivamente de seus registros médicos. Marcos motores globais e idade motora equivalente foram usados para descrever o desenvolvimento motor. Avaliação padronizada do neurodesenvolvimento e a Escala Bayley de Desenvolvimento Infantil definiram o desenvolvimento global. A Escala Peabody de Desenvolvimento Motor, o Teste de Proficiência Motora de Bruininks-Oseretsky, e o Teste Desenvolvimental de Beery-Buktenica para Integração Visuo-motora foram usados para descrever o desenvolvimento em domínios motores específicos. RESULTADOS: Crianças com síndrome de Dravet mostraram atraso no sentar (sete em 14) e no andar independente (11 em 25). A idade motora global equivalente revelou atraso em 29 de 38 avaliações (idade 9-115m). Todas as avaliações de crianças com mais de 2 anos (16 de 16) mostraram atraso. O atraso motor global estava presente em sete de sete, e motor fino em 10 de 13 avaliações (idade 19-167m). INTERPRETAÇÃO: O desenvolvimento motor é atrasado na maioria das crianças com síndrome de Dravet maiores do que 2 anos, e aumenta com a idade.

A shape-recovery polymer coating for the corrosion protection of metallic surfaces.

Self-healing polymer coatings are a type of smart material aimed for advanced corrosion protection of metals. This paper presents the synthesis and characterization of two new UV-cure self-healing coatings based on acrylated polycaprolactone polyurethanes. On a macroscopic scale, the cured films all show outstanding mechanical properties, combining relatively high Young's modulus of up to 270 MPa with a strain at break above 350%. After thermal activation the strained films recover up to 97% of their original length. Optical and electron microscopy reveals the self-healing properties of these coatings on hot dip galvanized steel with scratches and microindentations. The temperature-induced closing of such defects restores the corrosion protection and barrier properties of the coating as shown by electrochemical impedance spectroscopy and scanning vibrating electrode technique. Therefore, such coatings are a complementary option for encapsulation-based autonomous corrosion protection systems.