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BACKGROUND: We developed a gap analysis that examines the role of brain-computer interfaces (BCI) in patients with disorders of consciousness (DoC), focusing on their assessment, establishment of communication, and engagement with their environment. METHODS: The Curing Coma Campaign convened a Coma Science work group that included 16 clinicians and neuroscientists with expertise in DoC. The work group met online biweekly and performed a gap analysis of the primary question. RESULTS: We outline a roadmap for assessing BCI readiness in patients with DoC and for advancing the use of BCI devices in patients with DoC. Additionally, we discuss preliminary studies that inform development of BCI solutions for communication and assessment of readiness for use of BCIs in DoC study participants. Special emphasis is placed on the challenges posed by the complex pathophysiologies caused by heterogeneous brain injuries and their impact on neuronal signaling. The differences between one-way and two-way communication are specifically considered. Possible implanted and noninvasive BCI solutions for acute and chronic DoC in adult and pediatric populations are also addressed. CONCLUSIONS: We identify clinical and technical gaps hindering the use of BCI in patients with DoC in each of these contexts and provide a roadmap for research aimed at improving communication for adults and children with DoC, spanning the clinical spectrum from intensive care unit to chronic care.
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PURPOSE: Phosphatidylinositol Glycan Anchor Biosynthesis, class G (PIGG) is an ethanolamine phosphate transferase catalyzing the modification of glycosylphosphatidylinositol (GPI). GPI serves as an anchor on the cell membrane for surface proteins called GPI-anchored proteins (GPI-APs). Pathogenic variants in genes involved in the biosynthesis of GPI cause inherited GPI deficiency (IGD), which still needs to be further characterized. METHODS: We describe 22 individuals from 19 unrelated families with biallelic variants in PIGG. We analyzed GPI-AP surface levels on granulocytes and fibroblasts for three and two individuals, respectively. We demonstrated enzymatic activity defects for PIGG variants in vitro in a PIGG/PIGO double knockout system. RESULTS: Phenotypic analysis of reported individuals reveals shared PIGG deficiency-associated features. All tested GPI-APs were unchanged on granulocytes whereas CD73 level in fibroblasts was decreased. In addition to classic IGD symptoms such as hypotonia, intellectual disability/developmental delay (ID/DD), and seizures, individuals with PIGG variants of null or severely decreased activity showed cerebellar atrophy, various neurological manifestations, and mitochondrial dysfunction, a feature increasingly recognized in IGDs. Individuals with mildly decreased activity showed autism spectrum disorder. CONCLUSION: This in vitro system is a useful method to validate the pathogenicity of variants in PIGG and to study PIGG physiological functions.
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Trastorno del Espectro Autista , Discapacidad Intelectual , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Humanos , Proteínas de la Membrana , Linaje , Convulsiones , VirulenciaRESUMEN
PURPOSE OF REVIEW: The purpose of this review is to highlight the origin and evolution of the field of neurodevelopmental disabilities and describe the main construct(s) upon which the current classification of neurodevelopmental disorders is based. RECENT FINDINGS: We address the following questions: Are neurodevelopmental disorders independent entities? Why is it desirable to understand the neurobiological substrate for these disorders? What new knowledge have we generated by leveraging advances in neuroscience, genetics, and neuroimaging? And finally, is the current construct, that is based on functional classification, still useful? SUMMARY: As our biological understanding of brain-behavior disorders evolves, we ought to re-evaluate the current classification system and expand it into a multidimensional classification that takes into account behavioral profiles and underlying mechanisms.
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Encéfalo/diagnóstico por imagen , Trastornos del Neurodesarrollo/diagnóstico , Humanos , Trastornos del Neurodesarrollo/clasificación , Trastornos del Neurodesarrollo/diagnóstico por imagen , NeuroimagenRESUMEN
While prefrontal cortex dysfunction has been implicated in high food cravings, other cortical regions, like the parietal cortex, are potentially also involved in regulating craving. This study explored the effects of stimulating the inferior parietal lobule (IPL) and dorsolateral prefrontal cortex (DLPFC) on food craving state and trait. Transcranial direct current stimulation (tDCS) was administered at 1.5 mA for 5 consecutive days. Participants received 20 min of IPL, DLPFC, or sham stimulation (SHAM) each day which consisted of two rounds of 10-min stimulation, divided by a 10-min mindfulness task break. In addition, we studied inhibition and subjective psychological aspects like body image and self-esteem state and trait. To decompose immediate and cumulative effects, we measured the following on days 1 and 5: inhibition through the Go/No-go task; and food craving, self-esteem, and body appreciation through a battery of questionnaires. We found that false alarm errors decreased in the participants receiving active stimulation in the DLPFC (DLPFC-group). In contrast, false alarm errors increased in participants receiving active stimulation in the IPL (IPL-group). At the same time, no change was found in the participants receiving SHAM (SHAM-group). There was a trending reduction in craving trait in all groups. Momentary craving was decreased in the DLPFC-group and increased in IPL-group, yet a statistical difference was not reached. According to time and baseline, self-esteem and body perception improved in the IPL-group. Furthermore, self-esteem trait significantly improved over time in the DLPFC-group and IPL-group. These preliminary results indicate that tDCS modulates inhibition in frontoparietal areas with opposite effects, enhancing it in DLPFC and impairing it in IPL. Moreover, craving is moderately linked to inhibition, self-esteem, and body appreciation which seem not to be affected by neuromodulation but may rely instead on broader regions as more complex constructs. Finally, the fractionated protocol can effectively influence inhibition with milder effects on other constructs.
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SUMMARY: The diagnosis and management of disorders of consciousness in children continue to present a clinical, research, and ethical challenge. Though the practice guidelines for diagnosis and management of disorders of consciousness in adults are supported by decades of empirical and pragmatic evidence, similar guidelines for infants and children are lacking. The maturing conscious experience and the limited behavioral repertoire to report consciousness in this age group restrict extrapolation from the adult literature. Equally challenging is the process of heightened structural and functional neuroplasticity in the developing brain, which adds a layer of complexity to the investigation of the neural correlates of consciousness in infants and children. This review discusses the clinical assessment of pediatric disorders of consciousness and delineates the diagnostic and prognostic utility of neurophysiological and neuroimaging correlates of consciousness. The potential relevance of these correlates for the developing brain based on existing theoretical models of consciousness in adults is outlined.
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Trastornos de la Conciencia , Estado de Conciencia , Adulto , Encéfalo/diagnóstico por imagen , Niño , Trastornos de la Conciencia/diagnóstico , Humanos , Neuroimagen , PronósticoRESUMEN
In this review, we report a case of an adolescent girl presenting with epileptic encephalopathy preceded by febrile illness, demarcate the clinical phenotypic homogeneity among previously reported cases, and hypothesize on potential mechanisms based on current experimental evidence. Our literature review revealed >249 cases that share several main features: febrile illness with no preceding condition, negative laboratory studies including cerebrospinal fluid (CSF) analysis, status epilepticus refractory to conventional pharmacotherapy, and long-term developmental delays. This condition appears to have many names, the most recent of which is "FIRES" (fever-induced refractory epileptic encephalopathy). It seems likely that the described cases are representing the same entity. The possibility of a genetic or acquired channelopathy can be raised in light of negative infectious, autoimmune, microscopic, and gross pathology findings.
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Epilepsia/diagnóstico , Terminología como Asunto , Adolescente , Adulto , Niño , Preescolar , Electroencefalografía , Epilepsia/clasificación , Epilepsia Parcial Compleja/clasificación , Epilepsia Parcial Compleja/diagnóstico , Epilepsia Tónico-Clónica/clasificación , Epilepsia Tónico-Clónica/diagnóstico , Femenino , Humanos , Persona de Mediana Edad , Convulsiones Febriles/clasificación , Convulsiones Febriles/diagnóstico , Estado Epiléptico/clasificación , Estado Epiléptico/diagnóstico , Adulto JovenRESUMEN
In this chapter, we highlight the various definitions of early brain plasticity commonly used in the scientific literature. We then present a conceptual framework of early brain plasticity that focuses on plasticity at the level of the synapse (synaptic plasticity) and the level of the network (connectivity). The proposed framework is organized around three main domains through which current theories and principles of early brain plasticity can be integrated: (1) the mechanisms of plasticity and constraints at the synaptic level and network connectivity, (2) the importance of temporal considerations related to the development of the immature brain, and (3) the functions early brain plasticity serve. We then apply this framework to discuss some clinical disorders caused by and/or associated with impaired plasticity mechanisms. We propose that a careful examination of the relationship between mechanisms, constraints, and functions of early brain plasticity in health and disease may provide an integrative understanding of the current theories and principles generated by experimental and observational studies.
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Encéfalo , Plasticidad Neuronal , Humanos , SinapsisRESUMEN
The nervous system is vulnerable to intrinsic and extrinsic metabolic perturbations. In particular, the cerebellum, with its large Purkinje cells and its high density of neurons and glial cells, has high metabolic demand and is highly vulnerable to metabolic derangements. As a result, many disorders of intermediary metabolism will preferentially and sometimes selectively target the cerebellum. However, many of these disorders present in a multisystem fashion with ataxia being a part of the neurologic symptom complex. The presentation of these disorders depends on the time of onset and type of metabolic derangement. Early infantile or intrauterine-onset diseases will present in a young child typically with global hypotonia and both nystagmus and ataxia become more apparent later in life, while later-onset diseases usually present primarily with ataxia. It is important to note that the majority of these disorders are progressive if they are untreated. This chapter provides a review of acquired and genetic metabolic disorders that target the cerebellum, and discusses their diagnostic evaluation and therapy.
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Ataxia/complicaciones , Cerebelo/anomalías , Cerebelo/patología , Enfermedades Metabólicas/complicaciones , Ataxia/diagnóstico por imagen , Ataxia/patología , Ataxia/terapia , Cerebelo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Enfermedades Metabólicas/diagnóstico por imagen , Enfermedades Metabólicas/genética , Enfermedades Metabólicas/terapiaRESUMEN
We delineate the clinical characteristics, incidence, and prevalence of pediatric-onset multiple sclerosis in Abu Dhabi, United Arab Emirates, from 2010 to 2014. Eighty-two patients (65% female) were identified. Fifty-three (64.6%) were Emiratis (45 from Abu Dhabi and 8 from 5 other emirates) and 29 were expatriates. Mean age of onset was 15.9 years overall, 15.3 years in males and 16.3 years in females. Patients with onset before age 12 years presented with visual symptoms while those with onset after age 12 years presented with a mixture of visual, motor and sensory symptoms. Interferon beta-1a was the most frequently used disease-modifying therapy (48%). In Abu Dhabi Emirati nationals, the age- and sex-adjusted prevalences were 26/100 000 for males and 36/100 000 for females. The total incidence in Emirati nationals from 2010 to 2014 was 2.3/100 000 for ages 10 to 14 years and 7.2/100 000 for ages 15 to 19 years. By comparison with international cohorts, the incidence of pediatric-onset multiple sclerosis in Abu Dhabi is higher whereas gender distribution is similar.