Se narra la experiencia de una película en la cárcel inspirada en Pier Paolo Pasolini. NON È SOGNO (NO ES SUEÑO) es una película grabada con los presos de la cárcel de Capanne (Perugia) que comienza ...con los ensayos de una escena de Che cosa sono le nuvole? de Pasolini, aquella en la que Ninetto Davoli y Totò se preguntan acerca del juicio y la verdad. Un dispositivo pensado para crear un espacio lúdico, para romper la visión sobre “la cárcel de los otros”. La actuación se convierte en una puesta en escena de la vida, de la historia propia, actuación de una verdad humana.
Neurodevelopmental disorders affect motor, cognitive, language, learning, and behavioural development with lifelong consequences. Early identification of infants at risk for neurodevelopmental ...disorders is a major prerequisite for intervention programmes. This ensures that interventions which aim to positively modify the natural history of these disorders can start in the first weeks or months of life. As indicated by recent scientific evidence, gene abnormalities or congenital brain lesions are not the sole determinants for the neurodevelopmental outcome of affected infants. In fact, environment and experience may modify brain development and improve the outcome in infants at risk for neurodevelopmental disorders. In this review, we analyse the complexity and sensitivity of the brain to environmental stimuli, highlighting clinical effects of early intervention, mainly reported so far in preterm infants, and summarizing the effects of enriched environment on human and animal models. Finally, we discuss some new approaches to early intervention, based on recent neurophysiological theories and new breakthroughs in biotechnologies for diagnosis and rehabilitation.
What this paper adds
Evidence is reported for the contribution of newer neurophysiological models and animal studies to EI programs
ICT and biomechatronic tecniques can be of support for EI
The literature on time perception in individuals with ADHD is extensive but inconsistent, probably reflecting the use of different tasks and performances indexes. A sample of 40 children/adolescents ...(20 with ADHD, 20 neurotypical) was engaged in two identical psychophysical tasks measuring auditory time thresholds in the milliseconds (0.25-1 s) and seconds (0.75-3 s) ranges. Results showed a severe impairment in ADHD for milliseconds thresholds (Log10BF = 1.9). The deficit remained strong even when non-verbal IQ was regressed out and correlation with age suggests a developmental delay. In the seconds range, thresholds were indistinguishable between the two groups (Log10BF = - 0.5) and not correlated with milliseconds thresholds. Our results largely confirm previous evidence suggesting partially separate mechanisms for time perception in the ranges of milliseconds and seconds. Moreover, since the evidence suggests that time perception of milliseconds stimuli might load relatively less on cognitive control and working memory, compared to longer durations, the current results are consistent with a pure timing deficit in individuals with ADHD.
Aim
This systematic review evaluates the accuracy of clinical tools used at a corrected age of 6 months or younger to predict motor and cognitive delay (not cerebral palsy) at 24 months’ corrected ...age, in infants born very preterm.
Method
Six databases were searched. Quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies tool. Predictive analysis included calculation of sensitivity and specificity, inspection of summary receiver operating characteristics curves, and bivariate meta‐analysis.
Results
Six assessments were identified in 10 studies of 992 infants. Overall prevalence of motor delay was 13.8% and cognitive delay was 11.7%. Methodological quality was variable for patient selection, reference standard, flow, and timing. All studies had a low risk of bias for the index test. General Movement Assessment (GMA) predicted motor and cognitive outcomes with good accuracy for mild, moderate, and severe delays (fidgety age: pooled diagnostic odds ratio=12.3 5.9–29.8; hierarchical summary receiver operating characteristics curve=0.733). The Hammersmith Infant Neurological Examination (HINE) demonstrated excellent predictive accuracy for severe motor delay (3mo and 6mo; sensitivity 93% 68–100%, specificity 100% 96–100%) but showed limited ability to predict milder delays.
Interpretation
In the population of infants born very preterm, few assessment tools used at 6 months or younger corrected age have proven predictive accuracy for cognitive and motor delay at 24 months’ corrected age. Only the GMA and HINE demonstrated useful predictive validity.
What this paper adds
General movements have predictive validity for both motor and cognitive dysfunction in infants born very preterm.
The Hammersmith Infant Neurological Examination showed the highest predictive accuracy for severe motor delay.
The General Movement Assessment was the best tool to predict mild‐to‐moderate motor and cognitive delays.
Herramientas clínicas utilizadas en lactantes nacidos muy prematuros para predecir el retraso motor y cognitivo (no la parálisis cerebral): una revisión sistemática
Objetivo
Esta revisión sistemática evalúa la precisión de las herramientas clínicas utilizadas a una edad corregida de 6 meses o menos para predecir el retraso motor y cognitivo (no la parálisis cerebral) a los 24 meses de edad corregida, en bebés nacidos muy prematuros.
Método
Se realizaron búsquedas en seis bases de datos. La calidad se evaluó mediante la herramienta Evaluación de la calidad de los estudios de precisión diagnóstica. El análisis predictivo incluyó el cálculo de la sensibilidad y la especificidad, la inspección de las curvas de resumen de las características operativas del receptor y el metanálisis bivariado.
Resultados
Se identificaron seis evaluaciones en 10 estudios de 992 lactantes. La prevalencia global de retraso motor fue del 13,8% y el retraso cognitivo fue del 11,7%. La calidad metodológica fue variable para la selección de pacientes, estándar de referencia, flujo y tiempo. Todos los estudios tuvieron un bajo riesgo de sesgo para la prueba índice. La Evaluación de los Movimientos Generales (GMA) predijo resultados motores y cognitivos con buena precisión para retrasos leves, moderados y graves (edad movimientos inquietos: razón de posibilidades diagnósticas agrupadas = 12,3 5,9‐29,8; curva de características operativas resumidas jerárquicas del receptor = 0,733). El examen neurológico infantil de Hammersmith (HINE) demostró una precisión predictiva excelente para retrasos motores graves (3 meses y 6 meses; sensibilidad 93% 68‐100%, especificidad 100% 96‐100%) pero mostró una capacidad limitada para predecir retrasos más leves.
Interpretación
En la población de bebés nacidos muy prematuros, pocas herramientas de evaluación utilizadas a los 6 meses o antes de la edad corregida han demostrado una precisión predictiva para el retraso cognitivo y motor a los 24 meses de edad corregida. Solo la GMA y HINE demostraron una validez predictiva útil.
Instrumentos clínicos usados em crianças pequenas nascidas muito prematuras para predizer o atraso motor e cognitivo (não paralisia cerebral): uma revisão sistemática
Objetivo
Esta revisão sistemática avaliou a acurácia de ferramentas clínicas usadas na idade corrigida de 6 anos ou menos para predizer atraso motor e cognitivo (não paralisia cerebral) aos 24 meses de idade corrigida, em lactentes nascidos muito prematuros.
Método
Seis bases de dados foram pesquisadas. A qualidade foi avaliada usando a ferramenta Avaliação de qualidade de Estudos de Acurácia Diagnóstica. Análise preditiva incluiu o cálculo da sensibilidade e especificidade, inspeção da síntese das curvas to tipo “receiver operating” características, e metanálise bivariada.
Resultados
Seis avaliações foram identificadas em 10 estudos com 992 lactentes. A prevalência geral de atraso motor foi 13,8% e atraso cognitivo foi 11,7%. A qualidade metodológica foi variável para a seleção de pacientes, padrão de referência, fluxo e tempo. Todos os estudos tiveram baixo risco de viés. A General Movement Assessment (GMA) foi preditiva de resultados motores e cognitivos com boa acurácia para atrasos leves, moderados e severos (idade de fidgety: taxa de risco diagnóstico agrupado =12,3 5,9–29,8; síntese hierárquica da curva receiver operating característica =0,733). O Exame neurológico infantil de Hammersmith (HINE) demonstrou excelente acurácia preditiva para atraso motor severo (3m e 6m; sensibilidade 93% 68–100%, especificidade 100% 96–100%) mas mostrou capacidade limitada de predizer atrasos mais leves.
Interpretação
Na população de lactentes nascidos muito prematuros, poucos instrumentos de avaliação usados na idade de 6 meses de idade corrigida ou menos mostraram acurácia preditiva comprovada para atraso motor e cognitivo aos 24 meses de idade corrigida. Apenas a GMA e HINE demonstraram validade preditiva útil.
What this paper adds
General movements have predictive validity for both motor and cognitive dysfunction in infants born very preterm.
The Hammersmith Infant Neurological Examination showed the highest predictive accuracy for severe motor delay.
The General Movement Assessment was the best tool to predict mild‐to‐moderate motor and cognitive delays.
This article's has been translated into Spanish and Portuguese.
Follow the links from the to view the translations.
Unilateral Cerebral Palsy (UCP), the most frequent form of Cerebral Palsy, usually affects more the upper limb (UL) than the lower limb. Rehabilitation programs are addressed to improve manual ...abilities and UL use. In recent years, Information and Communication Technology (ICT) has been introduced in rehabilitation to increase treatment opportunities for patients, and also in home-based intervention. Moreover, the discovery of the Mirror Neuron System allowed to insert a new paradigm of treatment that is the Action Observation Training (AOT). The aim of the present study was to investigate the feasibility of a new rehabilitative home-based approach, called Tele-UPCAT (Tele-monitored UPper Limb Children Action Observation Training), based on the principles of AOT, in a group of Italian children and adolescents with UCP. This investigation was to provide information about the possibility of introducing ICT in telerehabilitation field. Twenty-nine children aged 11.73 ± 3.65 years (range 6.00-18.75) with a diagnosis of UCP participated in the study. They carried out 15 days of training based on the AOT paradigm with Tele-UPCAT system while wearing Actigraphs on both wrists. The feasibility of both training and study design and procedures was assessed through nine criteria taken from existent literature and from a questionnaire designed and realized
for the purpose, based on standard items of usability and acceptability. All feasibility criteria were met: 80% of training sessions were completed in the planned time and no significant technical issues were found. From the questionnaire, total scores were all above 82.15%, while the four sections obtained the following scores: (i) customization of exercises 80.00%; (ii) acceptability at home, 77.50%; (iii) required effort 80.00%; and (iv) suitability of manual and software 95.00%. No differences were found for age and sex. Tele-UPCAT demonstrated to be feasible as a home-based AOT for children and adolescents with UCP. Trial registration NCT03094455.
Multisensory processes permit combinations of several inputs, coming from different sensory systems, allowing for a coherent representation of biological events and facilitating adaptation to ...environment. For these reasons, their application in neurological and neuropsychological rehabilitation has been enhanced in the last decades. Recent studies on animals and human models have indicated that, on one hand multisensory integration matures gradually during post-natal life and development is closely linked to environment and experience and, on the other hand, that modality-specific information seems to do not benefit by redundancy across multiple sense modalities and is more readily perceived in unimodal than in multimodal stimulation. In this review, multisensory process development is analyzed, highlighting clinical effects in animal and human models of its manipulation for rehabilitation of sensory disorders. In addition, new methods of early intervention based on multisensory-based rehabilitation approach and their applications on different infant populations at risk of neurodevelopmental disabilities are discussed.
Summary
Creatine metabolism disorders include guanidinoacetate methyltransferase (GAMT) deficiency, arginine:glycine amidinotransferase (AGAT) deficiency, and the creatine transporter (CT1‐encoded by ...SLC6A8 gene) deficiency. Epilepsy is one of the main symptoms in GAMT and CT1 deficiency, whereas the occurrence of febrile convulsions in infancy is a relatively common presenting symptom in all the three above‐mentioned diseases. GAMT deficiency results in a severe early onset epileptic encephalopathy with development arrest, neurologic deterioration, drug‐resistant seizures, movement disorders, mental disability, and autistic‐like behavior. In this disorder, epilepsy and associated abnormalities on electroencephalography (EEG) are more responsive to substitutive treatment with creatine monohydrate than to conventional antiepileptic drugs. AGAT deficiency is mainly characterized by mental retardation and severe language disorder without epilepsy. In CT1 deficiency epilepsy is generally less severe than in GAMT deficiency. All creatine disorders can be investigated through measurement of creatine metabolites in body fluids, brain proton magnetic resonance spectroscopy (1H‐MRS), and molecular genetic techniques. Blood guanidinoacetic acid (GAA) assessment and brain H‐MRS examination should be part of diagnostic workup for all patients presenting with epileptic encephalopathy of unknown origin. In girls with learning and/or intellectual disabilities with or without epilepsy, SLC6A8 gene assessment should be part of the diagnostic procedures. The aims of this review are the following: (1) to describe the electroclinical features of epilepsy occurring in inborn errors of creatine metabolism; and (2) to delineate the metabolic alterations associated with GAMT, AGAT, and CT1 deficiency and the role of a substitutive therapeutic approach on their clinical and electroencephalographic epileptic patterns.
Abstract Down syndrome (DS), the most common genetic disorder associated with intellectual disabilities, is an untreatable condition characterized by a number of developmental defects and permanent ...deficits in the adulthood. Ts65Dn mice, the major animal model for DS, display severe cognitive and synaptic plasticity defects closely resembling the human phenotype. Here, we employed a multidisciplinary approach to investigate, for the first time in developing Ts65Dn mice, the effects elicited by early environmental enrichment (EE) on brain maturation and function. We report that exposure to EE resulted in a robust increase in maternal care levels displayed by Ts65Dn mothers and led to a normalization of declarative memory abilities and hippocampal plasticity in trisomic offspring. The positive effects of EE on Ts65Dn phenotype were not limited to the cognitive domain, but also included a rescue of visual system maturation. The beneficial EE effects were accompanied by increased BDNF and correction of over-expression of the GABA vesicular transporter vGAT. These findings highlight the beneficial impact of early environmental stimuli and their potential for application in the treatment of major functional deficits in children with DS.
Transcranial Direct Current Stimulation (tDCS) is an emerging tool to improve upper limb motor functions after stroke acquired in adulthood; however, there is a paucity of reports on its efficacy for ...upper limb motor rehabilitation in congenital or early-acquired stroke. In this pilot study we have explored, for the first time, the immediate effects, and their short-term persistence, of a single application of anodal tDCS on chronic upper limb motor disorders in children and young individuals with Unilateral Cerebral Palsy (UCP). To this aim, in a crossover sham-controlled study, eight subjects aged 10-28 years with UCP underwent two sessions of active and sham tDCS. Anodal tDCS (1.5 mA, 20 min) was delivered over the primary motor cortex (M1) of the ipsilesional hemisphere. Results showed, only following the active stimulation, an immediate improvement in unimanual gross motor dexterity of hemiplegic, but not of nonhemiplegic, hand in Box and Block test (BBT). Such improvement remained stable for at least 90 minutes. Performance of both hands in Hand Grip Strength test was not modified by anodal tDCS. Improvement in BBT was unrelated to participants’ age or lesion size, as revealed by MRI data analysis. No serious adverse effects occurred after tDCS; some mild and transient side effects (e.g., headache, tingling, and itchiness) were reported in a limited number of cases. This study provides an innovative contribution to scientific literature on the efficacy and safety of anodal tDCS in UCP. This trial is registered with NCT03137940.
Constitutional heterozygous mutations of ATP1A2 and ATP1A3, encoding for two distinct isoforms of the Na+/K+-ATPase (NKA) alpha-subunit, have been associated with familial hemiplegic migraine ...(ATP1A2), alternating hemiplegia of childhood (ATP1A2/A3), rapid-onset dystonia-parkinsonism, cerebellar ataxia-areflexia-progressive optic atrophy, and relapsing encephalopathy with cerebellar ataxia (all ATP1A3). A few reports have described single individuals with heterozygous mutations of ATP1A2/A3 associated with severe childhood epilepsies. Early lethal hydrops fetalis, arthrogryposis, microcephaly, and polymicrogyria have been associated with homozygous truncating mutations in ATP1A2. We investigated the genetic causes of developmental and epileptic encephalopathies variably associated with malformations of cortical development in a large cohort and identified 22 patients with de novo or inherited heterozygous ATP1A2/A3 mutations. We characterized clinical, neuroimaging and neuropathological findings, performed in silico and in vitro assays of the mutations' effects on the NKA-pump function, and studied genotype-phenotype correlations. Twenty-two patients harboured 19 distinct heterozygous mutations of ATP1A2 (six patients, five mutations) and ATP1A3 (16 patients, 14 mutations, including a mosaic individual). Polymicrogyria occurred in 10 (45%) patients, showing a mainly bilateral perisylvian pattern. Most patients manifested early, often neonatal, onset seizures with a multifocal or migrating pattern. A distinctive, 'profound' phenotype, featuring polymicrogyria or progressive brain atrophy and epilepsy, resulted in early lethality in seven patients (32%). In silico evaluation predicted all mutations to be detrimental. We tested 14 mutations in transfected COS-1 cells and demonstrated impaired NKA-pump activity, consistent with severe loss of function. Genotype-phenotype analysis suggested a link between the most severe phenotypes and lack of COS-1 cell survival, and also revealed a wide continuum of severity distributed across mutations that variably impair NKA-pump activity. We performed neuropathological analysis of the whole brain in two individuals with polymicrogyria respectively related to a heterozygous ATP1A3 mutation and a homozygous ATP1A2 mutation and found close similarities with findings suggesting a mainly neural pathogenesis, compounded by vascular and leptomeningeal abnormalities. Combining our report with other studies, we estimate that ∼5% of mutations in ATP1A2 and 12% in ATP1A3 can be associated with the severe and novel phenotypes that we describe here. Notably, a few of these mutations were associated with more than one phenotype. These findings assign novel, 'profound' and early lethal phenotypes of developmental and epileptic encephalopathies and polymicrogyria to the phenotypic spectrum associated with heterozygous ATP1A2/A3 mutations and indicate that severely impaired NKA pump function can disrupt brain morphogenesis.
PDF
