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Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.brainchart.io/ ). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.
Assuntos
Encéfalo , Longevidade , Estatura , Encéfalo/anatomia & histologia , Humanos , Imageamento por Ressonância Magnética/métodos , NeuroimagemRESUMO
Only a small number of studies have assessed structural differences between the two hemispheres during childhood and adolescence. However, the existing findings lack consistency or are restricted to a particular brain region, a specific brain feature, or a relatively narrow age range. Here, we investigated associations between brain asymmetry and age as well as sex in one of the largest pediatric samples to date (n = 4265), aged 1-18 years, scanned at 69 sites participating in the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. Our study revealed that significant brain asymmetries already exist in childhood, but their magnitude and direction depend on the brain region examined and the morphometric measurement used (cortical volume or thickness, regional surface area, or subcortical volume). With respect to effects of age, some asymmetries became weaker over time while others became stronger; sometimes they even reversed direction. With respect to sex differences, the total number of regions exhibiting significant asymmetries was larger in females than in males, while the total number of measurements indicating significant asymmetries was larger in males (as we obtained more than one measurement per cortical region). The magnitude of the significant asymmetries was also greater in males. However, effect sizes for both age effects and sex differences were small. Taken together, these findings suggest that cerebral asymmetries are an inherent organizational pattern of the brain that manifests early in life. Overall, brain asymmetry appears to be relatively stable throughout childhood and adolescence, with some differential effects in males and females.
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Encéfalo , Imageamento por Ressonância Magnética , Caracteres Sexuais , Humanos , Adolescente , Masculino , Criança , Feminino , Pré-Escolar , Lactente , Encéfalo/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , Encéfalo/anatomia & histologia , Fatores Etários , Desenvolvimento Infantil/fisiologia , Lateralidade Funcional/fisiologia , Desenvolvimento do Adolescente/fisiologiaRESUMO
BACKGROUND AND PURPOSE: Migraine has long been associated with unsteadiness and dizziness but postural control has not been studied in the ictal state. Here, the stability of upright stance during migraine attacks was measured. METHODS: Static balance was assessed prospectively in migraine patients (n = 30) during quiet stance for 40 s on a posturographic force platform. Recordings were performed both ictally and in the pain-free interval. Subjects were assessed under four different conditions yielding different visual and proprioceptive feedback environments. Both ictal and interictal data were compared with age-matched healthy controls (n = 30). RESULTS: Postural instability increased significantly under all experimental conditions during migraine attacks. Whilst standing on a foam pad with eyes closed, median sway area was 353 mm2 in control subjects, 318 mm2 in migraineurs in the pain-free period and 618 mm2 in the ictal state. However, Romberg and vestibular Romberg quotients were not altered during migraine attacks. Spectral analyses of postural sway also showed similar profiles in migraineurs and controls. The severity of headache was inversely correlated to Romberg quotients. CONCLUSIONS: The demonstrated pattern of balance disorder during migraine attacks suggests a transient cerebellar dysfunction. Our findings also indicate that intense headache induces a re-weighting of sensory processing toward less dependence on visual and proprioceptive information.
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Tontura/complicações , Enxaqueca sem Aura/complicações , Equilíbrio Postural/fisiologia , Propriocepção/fisiologia , Vertigem/complicações , Adulto , Tontura/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Enxaqueca sem Aura/fisiopatologia , Vertigem/fisiopatologia , Adulto JovemRESUMO
Autism is a heritable disorder, with over 250 associated genes identified to date, yet no single gene accounts for >1-2% of cases. The clinical presentation, behavioural symptoms, imaging and histopathology findings are strikingly heterogeneous. A more complete understanding of autism can be obtained by examining multiple genetic or behavioural mouse models of autism using magnetic resonance imaging (MRI)-based neuroanatomical phenotyping. Twenty-six different mouse models were examined and the consistently found abnormal brain regions across models were parieto-temporal lobe, cerebellar cortex, frontal lobe, hypothalamus and striatum. These models separated into three distinct clusters, two of which can be linked to the under and over-connectivity found in autism. These clusters also identified previously unknown connections between Nrxn1α, En2 and Fmr1; Nlgn3, BTBR and Slc6A4; and also between X monosomy and Mecp2. With no single treatment for autism found, clustering autism using neuroanatomy and identifying these strong connections may prove to be a crucial step in predicting treatment response.
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Transtorno Autístico/patologia , Encéfalo/patologia , Modelos Animais de Doenças , Família Multigênica/genética , Animais , Transtorno Autístico/genética , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos TransgênicosRESUMO
PURPOSE: The aim of the study was to assess the eftect ot the addition or iow-cose numan cnononic gonauoiropm (hCG) to ovarian stimulation with recombinant follicle stimulating hormone (rFSH) on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcome. MATERIALS AND METHODS: This retrospective clinical study was conducted on 141 women undergoing ICSI through a short GnRH-agonist protocol with rFSH and the addition of low-dose (100 IU/day) hCG. The control group consisted of 124 women undergoing ovarian stimulation with a similar protocol devoid of hCG. Statistical analysis in the study population along with a subgroup analysis for age 35 years and 36 years was performed. RESULTS: Women in hCG group were statistically significant older and with higher basal FSH compared to control group. This can be attributed to the Centre's latent tendency to add hCG in the stimulation protocol in poor prognosis patients. Despite this fact and the fact that several ovarian stimulation parameters, such as peak estradiol levels, number of oocytes retrieved, number of mature oocytes, and fertilization rates were in favor of the control group, the quality of transferred embryos and pregnancy rates were in favor of hCG group. Similar results were obtained in the subgroup analyses apart from peak estradiol levels, which did not differ among the study groups. CONCLUSIONS: The addition of hCG to rFSH may be associated with better quality embryos and higher pregnancy rates, even in women of advanced reproductive age with higher basal FSH levels, which are often considered to have poorer ovarian reserve.
Assuntos
Busserrelina/uso terapêutico , Gonadotropina Coriônica/administração & dosagem , Fármacos para a Fertilidade Feminina/uso terapêutico , Hormônio Foliculoestimulante Humano/uso terapêutico , Infertilidade Feminina/terapia , Indução da Ovulação/métodos , Substâncias para o Controle da Reprodução/administração & dosagem , Adulto , Quimioterapia Combinada , Transferência Embrionária , Feminino , Fertilização in vitro/métodos , Hormônio Liberador de Gonadotropina/agonistas , Humanos , Idade Materna , Oócitos , Gravidez , Taxa de Gravidez , Proteínas Recombinantes , Estudos Retrospectivos , Injeções de Esperma Intracitoplásmicas/métodosRESUMO
A 32-year-old woman with relapsing-remitting multiple sclerosis and a right optic neuritis with incomplete remission presented with unique neuro-ophthalmologic abnormality consisting of a spontaneous, pendular, vertical movement of the right eye consistent with the Heimann-Bielschowsky phenomenon (HBP). This rare form of dissociated nystagmus probably reflects a "dual abnormality mechanism" comprising the coexistence of an asymmetric conduction delay in the optic nerve and a strategic network disruption in brainstem gaze holding centres. For the clinician it is important to recognize this rare neuro-ophthalmologic syndrome and be aware of its benign nature.
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Nistagmo Patológico , Neurite Óptica , Adulto , Tronco Encefálico , Movimentos Oculares , Feminino , Humanos , Neurite Óptica/complicaçõesRESUMO
BACKGROUND AND PURPOSE: Although hypercoagulability-induced thromboembolism is generally accepted as cause of cerebral ischaemia in thalassemic patients, cardiogenic embolism has been recently suggested as another possible stroke etiology. METHODS: We present four adult ß-thalassemia major patients with manifest cardiac involvement who suffered territorial strokes. RESULTS: In the presence of siderotoxic cardiomyopathy and arrhythmia, we assumed cardiogenic embolism as etiology of stroke and initiated oral anticoagulation as preventive medication. Two of our patients were the first ß-thalassemia major patients who underwent successful thrombolysis with rtPA. CONCLUSIONS: Cardioembolism seems to be the cause of stroke in cases of ß-thalassemia major. Thrombolysis can be applied in the setting of acute brain ischaemia in such high risk patients.
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Anticoagulantes/uso terapêutico , Isquemia Encefálica/etiologia , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/uso terapêutico , Talassemia beta/complicações , Adulto , Antiarrítmicos/uso terapêutico , Afasia/etiologia , Fibrilação Atrial/etiologia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/tratamento farmacológico , Cardiomiopatias/etiologia , Cardiomiopatia Dilatada/complicações , Terapia por Quelação , Terapia Combinada , Feminino , Hemiplegia/etiologia , Hemossiderose/etiologia , Humanos , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/etiologia , Embolia Intracraniana/complicações , Masculino , Esplenectomia , Tomografia Computadorizada por Raios X , Reação Transfusional , Talassemia beta/tratamento farmacológico , Talassemia beta/cirurgia , Talassemia beta/terapiaRESUMO
Despite recent advances, the link between the evolution of atmospheric CO2 and climate during the Eocene greenhouse remains uncertain. In particular, modelling studies suggest that in order to achieve the global warmth that characterised the early Eocene, warmer climates must be more sensitive to CO2 forcing than colder climates. Here, we test this assertion in the geological record by combining a new high-resolution boron isotope-based CO2 record with novel estimates of Global Mean Temperature. We find that Equilibrium Climate Sensitivity (ECS) was indeed higher during the warmest intervals of the Eocene, agreeing well with recent model simulations, and declined through the Eocene as global climate cooled. These observations indicate that the canonical IPCC range of ECS (1.5 to 4.5 °C per doubling) is unlikely to be appropriate for high-CO2 warm climates of the past, and the state dependency of ECS may play an increasingly important role in determining the state of future climate as the Earth continues to warm.
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Muscle tremors reflect rhythmical motor unit (MU) activities. Therefore, the MU firing patterns and synchrony determine the properties of the parkinsonian force tremor (FT) and the neurogenic components of associated limb tremors. They may also be indicative of the neural mechanisms of tremor genesis which to date remain uncertain. We examined these MU behaviours during isometric contractions of a finger muscle in 19 parkinsonian subjects. Our results reveal that the parkinsonian FT is abnormally large. Like the physiological FT, it is accompanied by in-phase rhythms in all MU activities. However, there exist two important differences. Firstly, the synchrony during the parkinsonian FT is stronger than the normal one and therefore contributes to the FT enhancement. Secondly, the synchronous MU components partly represent rhythmical sequences of spike doublets and triplets whose incidences directly reflect the differences of the MU firing rates to the FT frequency. According to our analyses, the latter frequency coincides with the MU recruitment rate. Consequently, the numerous medium- and small-sized active MUs contribute rhythmical twitch doublets and triplets, i.e. large force pulses, to the parkinsonian FT. The impact of this effect on the FT amplitude is found to predominate over the impact of the augmented synchrony. Importantly, apart from the rule governing the occurrence of doublets/triplets, the mean interspike intervals within such spike events are fairly fixed around 50 ms. Such regularities in MU activities may reflect properties of the neural input underlying the FT, and thus represent a basis for more focused studies of the generator(s) of parkinsonian tremors.
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Potenciais de Ação , Músculo Esquelético/fisiopatologia , Doença de Parkinson/fisiopatologia , Tremor/etiologia , Idoso , Idoso de 80 Anos ou mais , Eletromiografia , Feminino , Humanos , Contração Isométrica , Masculino , Pessoa de Meia-Idade , Atividade Motora , Neurônios Motores/fisiologia , Periodicidade , Recrutamento Neurofisiológico , Tremor/fisiopatologiaAssuntos
Esclerose Lateral Amiotrófica/etiologia , Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Psoriásica/complicações , Adalimumab , Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/fisiologiaRESUMO
Spinal and bulbar muscular atrophy (Kennedy's disease) has been associated with balance dysfunction and falls. However, postural control has not been studied quantitatively. Here, we quantified upright stance and aimed to disentangle the role of vestibular, proprioceptive and oculomotor deficits. Static balance was assessed in Kennedy patients (n = 7) during quiet stance on a force platform under different visual and proprioceptive feedback conditions. Vestibular function was assessed with the video head impulse test. Sural nerve neurography was employed to evaluate the severity of peripheral neuropathy. Also, horizontal saccades were recorded and quantified by the main sequence relationship. Posturographic analyses revealed significantly increased body sway, more pronounced in conditions with closed eyes, which was also reflected in the calculated Romberg indices. Horizontal vestibulo-ocular reflex gains were normal, i.e. > 0.75. In contrast, compound sensory nerve action potentials were markedly decreased in all patients (mean = 2.4 µV). Two patients showed slow saccades with increased exponential main sequence constants. We conclude that Kennedy patients exhibit severe deficits in quiet stance. Postural instability is greatest in conditions of absent vision with reduced proprioception being the main determinant of unsteadiness. Some patients show slowed saccadic eye movements suggesting a nuclear abducens neuronopathy.
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Atrofia Bulboespinal Ligada ao X/fisiopatologia , Equilíbrio Postural/fisiologia , Propriocepção/fisiologia , Movimentos Sacádicos/fisiologia , Doenças Vestibulares/fisiopatologia , Potenciais de Ação/fisiologia , Adulto , Estudos de Casos e Controles , Humanos , Masculino , Pessoa de Meia-Idade , Células Receptoras Sensoriais/fisiologia , Nervo Sural/fisiologiaRESUMO
BACKGROUND: Autism spectrum disorder (ASD) is a common and etiologically heterogeneous neurodevelopmental disorder. Although many genetic causes have been identified (> 200 ASD-risk genes), no single gene variant accounts for > 1% of all ASD cases. A role for epigenetic mechanisms in ASD etiology is supported by the fact that many ASD-risk genes function as epigenetic regulators and evidence that epigenetic dysregulation can interrupt normal brain development. Gene-specific DNAm profiles have been shown to assist in the interpretation of variants of unknown significance. Therefore, we investigated the epigenome in patients with ASD or two of the most common genomic variants conferring increased risk for ASD. Genome-wide DNA methylation (DNAm) was assessed using the Illumina Infinium HumanMethylation450 and MethylationEPIC arrays in blood from individuals with ASD of heterogeneous, undefined etiology (n = 52), and individuals with 16p11.2 deletions (16p11.2del, n = 9) or pathogenic variants in the chromatin modifier CHD8 (CHD8+/-, n = 7). RESULTS: DNAm patterns did not clearly distinguish heterogeneous ASD cases from controls. However, the homogeneous genetically-defined 16p11.2del and CHD8+/- subgroups each exhibited unique DNAm signatures that distinguished 16p11.2del or CHD8+/- individuals from each other and from heterogeneous ASD and control groups with high sensitivity and specificity. These signatures also classified additional 16p11.2del (n = 9) and CHD8 (n = 13) variants as pathogenic or benign. Our findings that DNAm alterations in each signature target unique genes in relevant biological pathways including neural development support their functional relevance. Furthermore, genes identified in our CHD8+/- DNAm signature in blood overlapped differentially expressed genes in CHD8+/- human-induced pluripotent cell-derived neurons and cerebral organoids from independent studies. CONCLUSIONS: DNAm signatures can provide clinical utility complementary to next-generation sequencing in the interpretation of variants of unknown significance. Our study constitutes a novel approach for ASD risk-associated molecular classification that elucidates the vital cross-talk between genetics and epigenetics in the etiology of ASD.
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Transtorno do Espectro Autista/genética , Transtorno Autístico/genética , Transtornos Cromossômicos/genética , Metilação de DNA , Proteínas de Ligação a DNA/genética , Estudo de Associação Genômica Ampla/métodos , Deficiência Intelectual/genética , Fatores de Transcrição/genética , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Deleção Cromossômica , Cromossomos Humanos Par 16/genética , Epigênese Genética , Feminino , Redes Reguladoras de Genes , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino , Sensibilidade e Especificidade , Análise de Sequência de DNARESUMO
Clinico-anatomical correlations in multiple sclerosis patients presenting with central positional vertigo are lacking. We report on a patient with acute onset positional vertigo mimicking benign paroxysmal positional vertigo with a single enhancing lesion in the inner part of the superior cerebellar peduncle, disclosed only after thin slice MR-imaging. This location appears to be a common cause of central positional vertigo and should be regarded as characteristic for demyelinating rather than vascular pathology. In cases presenting with positional nystagmus and vertigo without other cerebellar deficits one should look explicitly for signal abnormalities in the inner part of the superior cerebellar peduncle. High spatial resolution-MRI seems to be mandatory for lesion detection.
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Doenças Desmielinizantes/complicações , Vertigem/etiologia , Doença Aguda , Anti-Inflamatórios/uso terapêutico , Núcleos Cerebelares/patologia , Doenças Desmielinizantes/tratamento farmacológico , Doenças Desmielinizantes/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Nistagmo Fisiológico/fisiologia , Vertigem/tratamento farmacológico , Vestíbulo do Labirinto/fisiopatologia , Vômito/etiologiaRESUMO
The purpose of the current study was to examine how repetitive behaviour in Autism Spectrum Disorder (ASD) is related to intrinsic functional connectivity patterns in a number of large-scale, neural networks. Resting-state fMRI scans from thirty subjects with ASD and thirty-two age-matched, typically developing control subjects were analysed. Seed-to-voxel and ROI-to-ROI functional connectivity analyses were used to examine resting-state connectivity in a number of cortical and subcortical neural networks. Bivariate correlation analysis was performed to examine the relationship between repetitive behaviour scores from the Repetitive Behaviour Scale - Revised and intrinsic functional connectivity in ASD subjects. Compared to control subjects, ASD subjects displayed marked over-connectivity of the thalamus with several cortical sensory processing areas, as well as over-connectivity of the basal ganglia with somatosensory and motor cortices. Within the ASD group, significant correlations were found between functional connectivity patterns and total RBS-R scores as well as one principal component analysis-derived score from the RBS-R. These results suggest that thalamocortical resting-state connectivity is altered in individuals with ASD, and that resting-state functional connectivity is associated with ASD symptomatology.
Assuntos
Transtorno do Espectro Autista/fisiopatologia , Comportamento/fisiologia , Encéfalo/fisiopatologia , Rede Nervosa/fisiopatologia , Vias Neurais/fisiopatologia , Adolescente , Cognição/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Análise de Componente Principal/métodos , Descanso/fisiologiaRESUMO
BACKGROUND: In this follow-up study of approximately 18 months we assessed parameters of medical management in a sample of 70 patients suffering from benign paroxysmal positional vertigo. METHODS: Apart from demographic data, we evaluated the time interval from the appearance of the first symptoms until a diagnostic positional manoeuvre was performed, the efficacy of liberatory manoeuvres, the prescription of medication, the use of technical diagnostic resources and the relapse rate. RESULTS: None of the patients had received a diagnostic positioning test until then. Moreover, in one out of three cases a further unnecessary technical diagnostic procedure was carried out. There was a tendency for the right labyrinth to be more frequently affected, a fact that was statistically independent from age and sex, as well as from overall prognosis, which was characterized by a 15.6% recurrence rate. All patients with manifest positional nystagmus were successfully treated: 87.2% immediately after the repositioning manoeuvre and the rest within 10 days by self-performing Brandt-Daroff exercises. Our retrospective analysis revealed that, given a normal neuro-otological examination, a typical medical history without manifest positioning nystagmus leads safely to the correct diagnosis. CONCLUSION: The delay between the onset of symptoms and the diagnosis of BPPV is very often unduly long. A focused medical history may be diagnostic even in the absence of nystagmus during the Dix-Hallpike manoeuvre.
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Nistagmo Patológico/complicações , Nistagmo Patológico/diagnóstico , Nistagmo Fisiológico , Vertigem/complicações , Vertigem/diagnóstico , Testes de Função Vestibular/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Cancer cells present higher metabolic needs in comparison to their normal, non-neoplastic counterparts, consuming carbohydrates as a source of energy. Moreover, increased fatty acid biosynthesis is noted in many malignancies. In this regard, we investigated specific metabolic markers, the fatty acid synthase (FASN) which catalyzes fatty acid synthesis and the glucose transporter 1 (GLUT1) which promotes glucose transport through the cellular membrane, in normal endometrium, endometrial hyperplasia, and endometrial malignancy. METHODS: We examined the immunohistochemical expression of GLUT1 and FASN in 43 cases of endometrioid adenocarcinoma, 15 cases of serous endometrial carcinoma, eight cases of clear cell endometrial carcinoma, 11 cases of atypical hyperplasia / endometrial intraepithelial neoplasia, 17 cases of simple hyperplasia, and 20 cases of normal endometrium. RESULTS: We observed a gradual increase in the expression of both markers, progressing from benign clinical conditions to malignancy. The most notable finding concerned the difference of FASN immunoreactivity between atypical hyperplasia and grade 1 endometrioid adenocarcinoma (p =0.01). CONCLUSION: GLUT1 and FASN expression demonstrated a gradual increase when advancing from endometrial hyperplasia to carcinoma. These findings suggest that both GLUT1 and FASN immunohistochemistry might be used as an adjunct in the differentiation between atypical endometrial hyperplasia and endometrial carcinoma in complex cases. HIPPOKRATIA 2017, 21(4): 169-174.