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OBJECTIVE: To assess cognitive, behavioral, and adaptive functions in children and young adults with hemophilia treated according to contemporary standards of care. STUDY DESIGN: Evolving Treatment of Hemophilia's Impact on Neurodevelopment, Intelligence, and Other Cognitive Functions (eTHINK) is a US-based, prospective, cross-sectional, observational study (September 2018 through October 2019). Males (aged 1-21 years) with hemophilia A or B of any severity, with or without inhibitors, were eligible. Participants underwent neurologic examinations and age-appropriate neuropsychological assessments, including standardized tests/ratings scales of early development, cognition, emotional/behavioral adjustment, and adaptive skills. RESULTS: Five hundred and fifty-one males with hemophilia A (n = 433) or B (n = 101) were enrolled. Performance on cognitive tests was largely comparable with that of age-matched US population norms, although participants in certain age groups (4-5 and 10-21 years) performed worse on measures of attention and processing speed. Furthermore, adolescents and young adults and those with comorbid attention-deficit/hyperactivity disorder (ADHD; n = 64) reported more adaptive and executive function problems in daily life. Incidence of ADHD in adolescents (21%) was higher than expected in the general population. CONCLUSIONS: In general, males with hemophilia demonstrated age-appropriate intellectual, behavioral, and adaptive development. However, specific patient/age groups showed poorer attention performance and concerns for executive and adaptive development. This study established a normative data set for monitoring neurodevelopment in individuals with hemophilia and highlight the importance of screening and intervention for challenges with cognitive and adaptive skills in this population. CLINICAL TRIAL REGISTRATION: Evolving Treatment of Hemophilia's Impact on Neurodevelopment, Intelligence, and Other Cognitive Functions (eTHINK); NCT03660774; https://clinicaltrials.gov/ct2/show/NCT03660774.
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Hemofilia A , Humanos , Hemofilia A/complicaciones , Masculino , Adolescente , Niño , Estudios Transversales , Estudios Prospectivos , Adulto Joven , Preescolar , Lactante , Cognición , Pruebas Neuropsicológicas , Hemofilia B/complicaciones , Trastorno por Déficit de Atención con Hiperactividad , Función Ejecutiva , Adaptación PsicológicaRESUMEN
The short pre-M1 helix within the S1-M1 linker (also referred to as the pre-M1 linker) between the agonist-binding domain (ABD, S1) and the M1 transmembrane helix of the NMDA receptor (NMDAR) is devoid of missense variants within the healthy population but is a locus for de novo pathogenic variants associated with neurological disorders. Several de novo variants within this helix have been identified in patients presenting early in life with intellectual disability, developmental delay, and/or epilepsy. In this study, we evaluated functional properties for twenty variants within the pre-M1 linker in GRIN1, GRIN2A, and GRIN2B genes, including six novel missense variants. The effects of pre-M1 variants on agonist potency, sensitivity to endogenous allosteric modulators, response time course, channel open probability, and surface expression were assessed. Our data indicated that virtually all of the variants evaluated altered channel function, and multiple variants had profound functional consequences, which may contribute to the neurological conditions in the patients harboring the variants in this region. These data strongly suggest that the residues within the pre-M1 helix play a key role in channel gating and are highly intolerant to genetic variation.
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Epilepsia , Discapacidad Intelectual , Receptores de N-Metil-D-Aspartato , Humanos , Epilepsia/genética , Mutación Missense/genética , Receptores de N-Metil-D-Aspartato/metabolismoRESUMEN
OBJECTIVE: Individuals with neurodevelopmental disorders often report disturbances in the autonomic nervous system (ANS)-related behavioral regulation, such as sensory sensitivity, anxiety, and emotion dysregulation. Cranial electrotherapy stimulation (CES) is a method of non-invasive neuromodulation presumed to modify behavioral regulation abilities via ANS modulation. Here we examined the feasibility and preliminary effects of a 4-week CES intervention on behavioral regulation in a mixed neurodevelopmental cohort of children, adolescents, and young adults. METHODS: In this single-arm open-label study, 263 individuals aged 4-24 who were receiving clinical care were recruited. Participants received at-home CES treatment using an Alpha-Stim® AID CES device for 20 minutes per day, 5-7 days per week, for four weeks. Before and after the intervention, a parent-report assessment of sensory sensitivities, emotion dysregulation, and anxiety was administered. Adherence, side effects, and tolerance of the CES device were also evaluated at follow-up. RESULTS: Results showed a 75% completion rate, an average tolerance score of 68.2 (out of 100), and an average perceived satisfaction score of 58.8 (out of 100). Additionally, a comparison between pre- and post-CES treatment effects showed a significant reduction in sensory sensitivity, anxiety, and emotion dysregulation in participants following CES treatment. CONCLUSIONS: Results provide justification for future randomized control trials using CES in children and adolescents with behavioral dysregulation. SIGNIFICANCE: CES may be a useful therapeutic tool for alleviating behavioral dysregulation symptoms in children and adolescents with neurodevelopmental differences.
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Terapia por Estimulación Eléctrica , Trastornos del Neurodesarrollo , Adolescente , Niño , Adulto Joven , Humanos , Ansiedad/terapiaRESUMEN
OBJECTIVE: To characterize predictors of recovery and outcome following pediatric arterial ischemic stroke, hypothesizing that age influences recovery after stroke. METHODS: We studied children enrolled in the International Pediatric Stroke Study between January 1, 2003 and July 31, 2014 with 2-year follow-up after arterial ischemic stroke. Outcomes were defined at discharge by clinician grading and at 2 years by the Pediatric Stroke Outcome Measure. Demographic, clinical, and radiologic outcome predictors were examined. We defined changes in outcome from discharge to 2 years as recovery (improved outcome), emerging deficit (worse outcome), or no change. RESULTS: Our population consisted of 587 patients, including 174 with neonatal stroke and 413 with childhood stroke, with recurrent stroke in 8.2% of childhood patients. Moderate to severe neurological impairment was present in 9.4% of neonates versus 48.8% of children at discharge compared to 8.0% versus 24.7% after 2 years. Predictors of poor outcome included age between 28 days and 1 year (compared to neonates, odds ratio [OR] = 3.58, p < 0.05), underlying chronic disorder (OR = 2.23, p < 0.05), and involvement of both small and large vascular territories (OR = 2.84, p < 0.05). Recovery patterns differed, with emerging deficits more common in children <1 year of age (p < 0.05). INTERPRETATION: Outcomes after pediatric stroke are generally favorable, but moderate to severe neurological impairments are still common. Age between 28 days and 1 year appears to be a particularly vulnerable period. Understanding the timing and predictors of recovery will allow us to better counsel families and target therapies to improve outcomes after pediatric stroke. ANN NEUROL 2020;87:840-852.
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Accidente Cerebrovascular/terapia , Adolescente , Factores de Edad , Edad de Inicio , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Enfermedades del Sistema Nervioso/etiología , Valor Predictivo de las Pruebas , Pronóstico , Recuperación de la Función , Recurrencia , Sistema de Registros , Factores de Riesgo , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico por imagen , Resultado del TratamientoRESUMEN
Almost all of what is known about neurologic and cognitive development in hemophilia derives from the Hemophilia Growth and Development Study, conducted during an era when treatment regimens and comorbidities differed significantly from the current environment. Results suggested hemophilia and human immunodeficiency virus had independent effects, and hemophilia negatively impacts academic achievement, attention, and behavior. The introduction of prophylaxis treatment in hemophilia has created the need for re-evaluation of the effects of hemophilia on neurodevelopment and cognition. We outline the Evolving Treatment of Hemophilia's Impact on Neurodevelopment, Intelligence, and Other Cognitive Functions (NCT03660774) study, which aims to meet this need.
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Desarrollo Infantil , Discapacidades del Desarrollo/etiología , Hemofilia A/complicaciones , Hemofilia A/patología , Neuropsicología , Niño , Discapacidades del Desarrollo/patología , Hemofilia A/psicología , Humanos , Desempeño PsicomotorRESUMEN
AIM: Our aim was to characterize the sensory processing outcome following neonatal arterial ischemic stroke (NAIS) and identify neuroanatomical correlates of abnormal sensory processing. METHOD: We evaluated children with NAIS longitudinally at 12 months, 18 months, and/or 30 months in areas of cognitive, motor, and language development. We gathered sensory processing data using the Sensory Profile-2 Caregiver Questionnaire. These data were analyzed against early magnetic resonance imaging using a voxel-based approach. RESULTS: Eighteen children (10 males, 8 females) with NAIS were evaluated longitudinally, of which six exhibited atypical sensory processing. Children with sensory processing deficits had lower overall developmental scores in motor, cognitive, and language domains. Neuroanatomical correlates were identified in the posterior periventricular white matter extending superiorly into the supramarginal gyrus, and inferiorly into the fusiform and inferior temporal gyri. INTERPRETATION: Our results provide new evidence that children with NAIS may experience difficulty processing sensory information, which is most likely associated with injuries in the posterior periventricular white matter, supramarginal gyrus, fusiform gyrus, and posterior thalamic radiation. WHAT THIS PAPER ADDS: Atypical sensory processing is common in children with neonatal arterial ischemic stroke (NAIS). NAIS territories in sensory areas were correlated with atypical sensory processing behaviors. Children with NAIS may benefit from early interventions targeted toward sensory processing. Future research mapping NAIS injuries using early magnetic resonance imaging may predict long-term outcomes.
CORRELACIÓN NEUROANATÓMICA DE LOS DÉFICITS SENSORIALES EN NIÑOS CON INFARTO ISQUÉMICO ARTERIAL NEONATAL: OBJETIVO: Nuestro objetivo fue caracterizar los efectos el procesamiento sensorial posterior a un ictus isquémico arterial neonatal (IIAN) e identificar la relación neuroanatómica del procesamiento sensorial anormal. MÉTODO: Evaluamos longitudinalmente a niños con IIAN a los 12, 18 y/o 30 meses en áreas de desarrollo cognitivo, motor y lingüístico. Recopilamos los datos del procesamiento sensorial usando el Perfil Sensorial. Estos datos fueron analizados contra las imágenes de resonancia magnética temprana utilizando la técnica de voxel-based morphometry. RESULTADOS: Fueron evaluados longitudinalmente 18 niños (10 varones, 8 mujeres) con IIAN, de los cuales seis mostraron un procesamiento sensorial atípico. Los niños con déficit del procesamiento sensorial tuvieron puntuaciones menores del desarrollo general en los dominios motor, cognitivo y lingüístico. La correlación neuroanatómica fue identificada en la sustancia blanca periventricular posterior extendiéndose superiormente hacia el giro supramarginal e inferiormente dentro del giro fusiforme y el giro temporal inferior. INTERPRETACIÓN: Nuestros resultados proporcionan nuevas evidencias que los niños con IIAN pueden experimentar dificultades en el procesamiento de información sensorial, que está probablemente asociado con lesiones en la sustancia blanca periventricular posterior, giro supramarginal, giro fusiforme y la radiación talámica posterior.
CORRELATOS NEUROANATÔMICOS DOS DÉFICITS SENSORIAIS EM CRIANÇAS COM ACIDENTE VASCULAR CEREBRAL ISQUÊMICO NEONATAL: OBJETIVOS: Nosso objetivo foi avaliar os resultados de processamento sensorial após acidente vascular cerebral isquêmico neonatal (AVC-IN) e identificar correlatos neuroanatômicos de processamentos sensoriais anormais. MÉTODO: Foram avaliadas crianças com AVC-IN longitudinalmente com 12 meses, 18 meses, e /ou 30 meses nas áreas do desenvolvimento cognitivo, motor e linguagem. Obtivemos os dados do processamento sensorial utilizando o Perfil Sensorial. Os dados foram analisados através de imagens de ressonância magnética precoce utilizando uma abordagem baseada em Voxel. RESULTADOS: Dezoito crianças (10 meninos e 8 meninas) com AVC-IN foram avaliadas longitudinalmente, das quais seis exibiram processamento sensorial atípico. Crianças com déficits de processamento sensorial tiveram menor pontuação total nos domínios de desempenho motor, cognitivo, e de linguagem. Correlatos neuroanatômicos foram identificados na substancia branca periventricular posterior, estendendo-se superiormente até o giro supramarginal e inferiormente até o giro fusiforme, e giro temporal inferior. INTERPRETAÇÃO: Estes resultados proporcionam novas evidencias de que crianças com AVC-I possam apresentar dificuldades de processar informações sensoriais, o que está provavelmente associado com danos ocorridos na substancia branca periventricular posterior, giro supramarginal, giro fusiforme, e projeções talâmicas posteriores.
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Isquemia Encefálica/complicaciones , Enfermedades Arteriales Cerebrales/complicaciones , Lóbulo Parietal/patología , Trastornos de la Sensación/etiología , Trastornos de la Sensación/patología , Accidente Cerebrovascular/complicaciones , Lóbulo Temporal/patología , Sustancia Blanca/patología , Isquemia Encefálica/diagnóstico por imagen , Enfermedades Arteriales Cerebrales/diagnóstico por imagen , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Enfermedades del Recién Nacido , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Lóbulo Parietal/diagnóstico por imagen , Trastornos de la Sensación/diagnóstico por imagen , Accidente Cerebrovascular/diagnóstico por imagen , Lóbulo Temporal/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagenRESUMEN
The anterior temporal lobes (ATL) have been implicated in a range of cognitive functions including auditory and visual perception, language, semantic knowledge, and social-emotional processing. However, the anatomical relationships between the ATLs and the broader cortical networks that subserve these functions have not been fully elucidated. Using diffusion tensor imaging (DTI) and probabilistic tractography, we tested the hypothesis that functional segregation of information in the ATLs is reflected by distinct patterns of structural connectivity to regions outside the ATLs. We performed a parcellation of the ATLs bilaterally based on the degree of connectivity of each voxel with eight ipsilateral target regions known to be involved in various cognitive networks. Six discrete segments within each ATL showed preferential connectivity to one of the ipsilateral target regions, via four major fiber tracts (uncinate, inferior longitudinal, middle longitudinal, and arcuate fasciculi). Two noteworthy interhemispheric differences were observed: connections between the ATL and orbito-frontal areas were stronger in the right hemisphere, while the consistency of the connection between the ATL and the inferior frontal gyrus through the arcuate fasciculus was greater in the left hemisphere. Our findings support the hypothesis that distinct regions within the ATLs have anatomical connections to different cognitive networks. Hum Brain Mapp 37:2210-2222, 2016. © 2016 Wiley Periodicals, Inc.
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Imagen de Difusión por Resonancia Magnética , Lóbulo Temporal/diagnóstico por imagen , Anciano , Mapeo Encefálico , Imagen de Difusión Tensora , Femenino , Humanos , Masculino , Vías Nerviosas/diagnóstico por imagenRESUMEN
OBJECTIVE: Recent studies have reported evidence of human papillomavirus 16 (HPV-16) in a very high proportion of pathological specimens of focal cortical dysplasia type IIb, but not in control specimens, motivating the proposal that viral infection during fetal development may play a causal role in the pathogenesis of focal cortical dysplasias. However, the significance of the association between HPV infection and focal cortical dysplasia type IIb, and its reproducibility across surgical centers, remain unclear. Here we sought evidence for HPV-16 in an independent cohort of surgical specimens. METHODS: We identified 14 specimens of focal cortical dysplasia type IIb from a single surgical center between 1995 and 2013. Multiple methods were used to establish presence or absence of HPV, including DNA polymerase chain reaction, conventional in situ hybridization, chromogenic in situ hybridization, and immunohistochemistry for p16. RESULTS: We found no conclusive evidence of HPV in any of the specimens. All but 1 of the cases were negative by >1 method. INTERPRETATION: These results raise questions about the prevalence of HPV infection in focal cortical dysplasias and about its potential importance as a causative agent.
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ADN Viral/análisis , Papillomavirus Humano 16/aislamiento & purificación , Malformaciones del Desarrollo Cortical de Grupo I/virología , Adolescente , Adulto , Preescolar , Epilepsia , Femenino , Papillomavirus Humano 16/genética , Humanos , Inmunohistoquímica , Hibridación in Situ , Masculino , Malformaciones del Desarrollo Cortical de Grupo I/epidemiología , Persona de Mediana Edad , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Papillomaviridae/metabolismo , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , Reacción en Cadena de la Polimerasa , Proteínas Virales/metabolismo , Adulto JovenRESUMEN
OBJECTIVES: To describe the antiepileptic drug (AED) treatment of patients with early infantile epileptic encephalopathy due to KCNQ2 mutations during the neonatal phase and the first year of life. METHODS: We identified 15 patients and reviewed the electroclinical, neuroimaging, and AED treatment data. RESULTS: Seizure onset was between 1 and 4 days of age with daily tonic asymmetric, focal and clonic seizures in nine patients and status epilepticus in the remaining six. Electroencephalography (EEG) showed multifocal epileptiform abnormalities in nine patients and a burst-suppression pattern in six. All patients were trialed with adequate daily doses of several AEDs before they reached seizure freedom. Six patients (40%) achieved seizure control within 2 weeks of carbamazepine (CBZ) administration and five (33%) were seizure-free with phenytoin (PHT). The last four patients (27%) were successfully treated with topiramate (TPM) (two patients), levetiracetam (LEV) (one), and a combination of LEV with TPM (one). Most patients reached seizure freedom within the first year of life and remained seizure-free thereafter. Twelve patients had moderate-to-severe developmental delay at follow-up. However, the two patients whose seizures ceased within a few days of onset showed only mild cognitive impairment. SIGNIFICANCE: Our findings suggest that drugs acting on sodium channels including CBZ and PHT should be considered as first-line treatment in patients with KCNQ2 encephalopathy. Voltage-gated sodium and potassium channels co-localize at the neuronal membrane. Therefore, the efficacy of drugs acting as sodium-channel blockers could be linked to their modulating effect on both channels. The type of KCNQ2 mutation might influence AED response as well as developmental outcome. Early recognition of KCNQ2 encephalopathy followed by the most appropriate and effective treatment may be important for reducing the neurodevelopmental impairment associated with this disorder.
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Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Epilepsia/genética , Canal de Potasio KCNQ2/genética , Mutación/genética , Niño , Preescolar , Trastornos del Conocimiento/etiología , Electroencefalografía , Epilepsia/complicaciones , Femenino , Humanos , Lactante , Masculino , Trastornos del Movimiento/etiología , Neuroimagen , Farmacogenética , Estudios RetrospectivosRESUMEN
Pediatric stroke is associated with a range of maladaptive cognitive and behavioral outcomes that often require targeted intervention. Despite increasing research on neuropsychological outcomes over the past decade, evidence for effective therapies and interventions for the most commonly reported cognitive and behavioral challenges is still limited. The most widely prescribed interventions address more overt deficits in sensorimotor and speech/language functions, yet interventions for higher-order cognitive, linguistic and behavioral deficits are notably less defined. Moreover, concepts of rehabilitation in adult stroke cannot be easily translated directly to pediatric populations because the effect of stroke and recovery in the developing brain takes a very different course than in the mature brain. In pediatric stroke, neuropsychological deficits often emerge gradually over time necessitating a long-term approach to intervention. Furthermore, family and school context often play a much larger role. The goal of this review is to describe cognitive and behavioral interventions for perinatal and childhood stroke, as motor rehabilitation is covered elsewhere in this issue. We also discuss cognitive aspects of current rehabilitative therapies and technology. Acknowledging the current limited state of stroke-specific rehabilitation research in children, findings from pediatric acquired brain injury intervention and use of transdiagnostic approaches lend important insights. Because there is limited support for single domain (cognitive) trainings and translation of research rehabilitation programs to clinical practice can be challenging, the value of holistic multidisciplinary approaches to improve everyday function in children and adolescents following stroke is emphasized.
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Lesiones Encefálicas , Accidente Cerebrovascular , Adolescente , Adulto , Femenino , Embarazo , Niño , Humanos , Cognición , Accidente Cerebrovascular/complicaciones , Encéfalo , Terapia ConductistaRESUMEN
Nouns and verbs are fundamental grammatical building blocks of all languages. Studies of brain-damaged patients and healthy individuals have demonstrated that verb processing can be dissociated from noun processing at a neuroanatomical level. In cases where bilingual patients have a noun or verb deficit, the deficit has been observed in both languages. This suggests that the noun-verb distinction may be based on neural components that are common across languages. Here we investigated the cortical organization of grammatical categories in healthy, early Spanish-English bilinguals using functional magnetic resonance imaging (fMRI) in a morphophonological alternation task. Four regions showed greater activity for verbs than for nouns in both languages: left posterior middle temporal gyrus (LMTG), left middle frontal gyrus (LMFG), pre-supplementary motor area (pre-SMA), and right middle occipital gyrus (RMOG); no regions showed greater activation for nouns. Multi-voxel pattern analysis within verb-specific regions showed indistinguishable activity patterns for English and Spanish, indicating language-invariant bilingual processing. In LMTG and LMFG, patterns were more similar within than across grammatical category, both within and across languages, indicating language-invariant grammatical class information. These results suggest that the neural substrates underlying verb-specific processing are largely independent of language in bilinguals, both at the macroscopic neuroanatomical level and at the level of voxel activity patterns.
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Mapeo Encefálico , Multilingüismo , Percepción del Habla/fisiología , Encéfalo/fisiología , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Lenguaje , Imagen por Resonancia Magnética , Masculino , Semántica , Adulto JovenRESUMEN
Dyslexia is a neurodevelopmental disorder mainly defined by reading difficulties. During reading, individuals with dyslexia exhibit hypoactivity in left-lateralized language systems. Lower activity in one brain circuit can be accompanied by greater activity in another, and, here, we examined whether right-hemisphere-based emotional reactivity may be elevated in dyslexia. We measured emotional reactivity (i.e., facial behavior, physiological activity, and subjective experience) in 54 children ages 7-12 with (n = 32) and without (n = 22) dyslexia while they viewed emotion-inducing film clips. Participants also underwent task-free functional magnetic resonance imaging. Parents of children with dyslexia completed the Behavior Assessment System for Children, which assesses real-world behavior. During film viewing, children with dyslexia exhibited significantly greater reactivity in emotional facial behavior, skin conductance level, and respiration rate than those without dyslexia. Across the sample, greater emotional facial behavior correlated with stronger connectivity between right ventral anterior insula and right pregenual anterior cingulate cortex (pFWE<.05), key salience network hubs. In children with dyslexia, greater emotional facial behavior related to better real-world social skills and higher anxiety and depression. Our findings suggest there is heightened visceromotor emotional reactivity in dyslexia, which may lead to interpersonal strengths as well as affective vulnerabilities.
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Dislexia , Mapeo Encefálico , Niño , Emociones , Humanos , Lenguaje , Imagen por Resonancia Magnética , LecturaRESUMEN
OBJECTIVE: To determine that children with arterial ischemic stroke (AIS) due to an identifiable arteriopathy are distinct from those without arteriopathy and that each arteriopathy subtype has unique and recognizable clinical features. METHODS: We report a large, observational, multicenter cohort of children with AIS, age 1 month to 18 years, enrolled in the International Pediatric Stroke Study from 2003 to 2014. Clinical and demographic differences were compared by use of the Fisher exact test, with linear step-up permutation min-p adjustment for multiple comparisons. Exploratory analyses were conducted to evaluate differences between cases of AIS with and without arteriopathy and between arteriopathy subtypes. RESULTS: Of 2,127 children with AIS, 725 (34%) had arteriopathy (median age 7.45 years). Arteriopathy subtypes included dissection (27%), moyamoya (24.5%), focal cerebral arteriopathy-inflammatory subtype (FCA-i; 15%), diffuse cerebral vasculitis (15%), and nonspecific arteriopathy (18.5%). Children with arteriopathic AIS were more likely to present between 6 and 9 years of age (odds ratio [OR] 1.93, p = 0.029) with headache (OR 1.55, p = 0.023), multiple infarctions (OR 2.05, p < 0.001), sickle cell anemia (OR 2.9, p = 0.007), and head/neck trauma (OR 1.93, p = 0.018). Antithrombotic use and stroke recurrence were higher in children with arteriopathy. Among arteriopathy subtypes, dissection was associated with male sex, older age, headache, and anticoagulant use; FCA-i was associated with hemiparesis and single infarcts; moyamoya was associated with seizures and recurrent strokes; and vasculitis was associated with bilateral infarctions. CONCLUSION: Specific clinical profiles are associated with cerebral arteriopathies in children with AIS. These observations may be helpful indicators in guiding early diagnosis and defining subgroups who may benefit most from future therapeutic trials.
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Isquemia Encefálica/etiología , Enfermedades Arteriales Cerebrales/epidemiología , Adolescente , Edad de Inicio , Disección Aórtica/complicaciones , Disección Aórtica/epidemiología , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Isquemia Encefálica/epidemiología , Isquemia Encefálica/terapia , Enfermedades Arteriales Cerebrales/complicaciones , Infarto Cerebral/epidemiología , Infarto Cerebral/etiología , Niño , Preescolar , Femenino , Fibrinolíticos/uso terapéutico , Salud Global , Cefalea/epidemiología , Cefalea/etiología , Humanos , Lactante , Recién Nacido , Aneurisma Intracraneal/complicaciones , Aneurisma Intracraneal/epidemiología , Masculino , Estudios Prospectivos , Recurrencia , Sistema de Registros , Factores de Riesgo , Resultado del Tratamiento , Vasculitis del Sistema Nervioso Central/complicaciones , Vasculitis del Sistema Nervioso Central/epidemiologíaRESUMEN
There is increasing recognition of a relationship between regional variability in cerebral gyrification and neurodevelopment. Recent work in morphometric MRI has shown that the local gyrification index (lGI), a measure of regional brain folding, may be altered in certain neurodevelopmental disorders. Other studies report that the lGI generally decreases with age in adolescence and young adulthood; however, little is known about how these age-dependent differences in brain maturation occur in atypical neurodevelopment and mechanisms underlying gyrification, such as synaptic pruning. Organization and optimization of dendrites and axons connections across the brain might be driving gyrification and folding processes. In this study, we first assessed lGI differences in the left hemisphere in a cohort of 39 children with developmental dyslexia (DD) between the ages of 7 and 15â¯years in comparison to 56 typically developing controls (TDC). To better understand the microstructural basis of these changes, we next explored the relationship between lGI differences and cortical thickness and neurite morphology by applying neurite orientation dispersion and density imaging (NODDI). We identified significant differences in lGI between children with DD and TDC in left lateral temporal and middle frontal regions. Further, DD failed to show the expected age-related decreases in lGI in the same regions. Age-related differences in lGI in DD were not explained by differences in cortical thickness, but did correlate with NODDI neurite density and orientation dispersion index. Our findings suggest that gyrification changes in DD are related to abnormal neurite morphology, and are possibly an expression of differences in synaptic pruning.
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Mapeo Encefálico , Corteza Cerebral/patología , Dislexia/patología , Neuritas/patología , Adolescente , Factores de Edad , Corteza Cerebral/crecimiento & desarrollo , Corteza Cerebral/fisiopatología , Niño , Dislexia/diagnóstico , Dislexia/fisiopatología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Neuritas/fisiologíaRESUMEN
Global patterns of brain injury correlate with motor, cognitive, and language outcomes in survivors of neonatal encephalopathy (NE). However, it is still unclear whether local changes in brain structure predict specific deficits. We therefore examined whether differences in brain structure at 6 months of age are associated with neurodevelopmental outcomes in this population. We enrolled 32 children with NE, performed structural brain MR imaging at 6 months, and assessed neurodevelopmental outcomes at 30 months. All subjects underwent T1-weighted imaging at 3 T using a 3D IR-SPGR sequence. Images were normalized in intensity and nonlinearly registered to a template constructed specifically for this population, creating a deformation field map. We then used deformation based morphometry (DBM) to correlate variation in the local volume of gray and white matter with composite scores on the Bayley Scales of Infant and Toddler Development (Bayley-III) at 30 months. Our general linear model included gestational age, sex, birth weight, and treatment with hypothermia as covariates. Regional brain volume was significantly associated with language scores, particularly in perisylvian cortical regions including the left supramarginal gyrus, posterior superior and middle temporal gyri, and right insula, as well as inferior frontoparietal subcortical white matter. We did not find significant correlations between regional brain volume and motor or cognitive scale scores. We conclude that, in children with a history of NE, local changes in the volume of perisylvian gray and white matter at 6 months are correlated with language outcome at 30 months. Quantitative measures of brain volume on early MRI may help identify infants at risk for poor language outcomes.
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Encéfalo/diagnóstico por imagen , Discapacidades del Desarrollo/diagnóstico por imagen , Trastornos del Desarrollo del Lenguaje/diagnóstico por imagen , Lenguaje , Encéfalo/crecimiento & desarrollo , Mapeo Encefálico , Niño , Trastornos del Conocimiento/diagnóstico por imagen , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética/métodos , Masculino , Pruebas NeuropsicológicasRESUMEN
The ability to generate novel sentences depends on cognitive operations that specify the syntactic function of nouns, verbs, and other words retrieved from the mental lexicon. Although neuropsychological studies suggest that such operations rely on neural circuits distinct from those encoding word form and meaning, it has not been possible to characterize this distinction definitively with neuroimaging. We used functional magnetic resonance imaging (fMRI) to show that a brain area engaged in a given grammatical operation can be identified uniquely by a monotonic decrease in activation as that operation is repeated. We applied this methodology to identify areas involved selectively in the operation of inflection of nouns or verbs. By contrast, areas involved in processing word meaning do not show this monotonic adaptation across stimuli. These results are the first to demonstrate adaptation in the fMR signal evoked not by specific stimuli, but by well-defined cognitive linguistic operations.
RESUMEN
We studied the cognitive abilities of a 13-year-old deaf child, deprived of most linguistic input from late infancy, in a battery of tests designed to reveal the nature of numerical and geometrical abilities in the absence of a full linguistic system. Tests revealed widespread proficiency in basic symbolic and non-symbolic numerical computations involving the use of both exact and approximate numbers. Tests of spatial and geometrical abilities revealed an interesting patchwork of age-typical strengths and localized deficits. In particular, the child performed extremely well on navigation tasks involving geometrical or landmark information presented in isolation, but very poorly on otherwise similar tasks that required the combination of the two types of spatial information. Tests of number- and space-specific language revealed proficiency in the use of number words and deficits in the use of spatial terms. This case suggests that a full linguistic system is not necessary to reap the benefits of linguistic vocabulary on basic numerical tasks. Furthermore, it suggests that language plays an important role in the combination of mental representations of space.
Asunto(s)
Trastornos del Conocimiento/etiología , Sordera/complicaciones , Trastornos del Desarrollo del Lenguaje/etiología , Matemática , Trastornos de la Percepción/etiología , Percepción Espacial/fisiología , Adolescente , Humanos , Lingüística , Masculino , Examen NeurológicoAsunto(s)
Inmunoglobulina G/inmunología , Meningitis/inmunología , Meningitis/fisiopatología , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Femenino , Humanos , Factores Inmunológicos/uso terapéutico , Meningitis/tratamiento farmacológico , Persona de Mediana Edad , Recurrencia , RituximabRESUMEN
Categories like "noun" and "verb" represent the basic units of grammar in all human languages, and the retrieval of categorical information associated with words is an essential step in the production of grammatical speech. Studies of brain-damaged patients suggest that knowledge of nouns and verbs can be spared or impaired selectively; however, the neuroanatomical correlates of this dissociation are not well understood. We used event-related functional MRI to identify cortical regions that were active when English-speaking subjects produced nouns or verbs in the context of short phrases. Two regions, in the left prefrontal cortex and left superior parietal lobule, were selectively activated for verb trials compared with noun trials; one region in the left inferior temporal lobe was more active during noun production than verb production. We propose that these regions are involved in representing core conceptual properties of nouns and verbs.
Asunto(s)
Corteza Cerebral/anatomía & histología , Lenguaje , Habla , Adulto , Encéfalo/anatomía & histología , Encéfalo/fisiología , Mapeo Encefálico , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética/métodos , Masculino , Modelos Anatómicos , Modelos Neurológicos , Psicolingüística , Semántica , Factores de Tiempo , Conducta Verbal , VocabularioRESUMEN
Dissociations in the ability to produce words of different grammatical categories are well established in neuropsychology but have not been corroborated fully with evidence from brain imaging. Here we report on a PET study designed to reveal the anatomical correlates of grammatical processes involving nouns and verbs. German-speaking subjects were asked to produce either plural and singular nouns, or first-person plural and singular verbs. Verbs, relative to nouns, activated a left frontal cortical network, while the opposite contrast (nouns-verbs) showed greater activation in temporal regions bilaterally. Similar patterns emerged when subjects performed the task with pseudowords used as nouns or as verbs. These results converge with findings from lesion studies and suggest that grammatical category is an important dimension of organization for knowledge of language in the brain.