RESUMO
PCGF2 encodes the polycomb group ring finger 2 protein, a transcriptional repressor involved in cell proliferation, differentiation, and embryogenesis. PCGF2 is a component of the polycomb repressive complex 1 (PRC1), a multiprotein complex which controls gene silencing through histone modification and chromatin remodelling. We report the phenotypic characterization of 13 patients (11 unrelated individuals and a pair of monozygotic twins) with missense mutations in PCGF2. All the mutations affected the same highly conserved proline in PCGF2 and were de novo, excepting maternal mosaicism in one. The patients demonstrated a recognizable facial gestalt, intellectual disability, feeding problems, impaired growth, and a range of brain, cardiovascular, and skeletal abnormalities. Computer structural modeling suggests the substitutions alter an N-terminal loop of PCGF2 critical for histone biding. Mutant PCGF2 may have dominant-negative effects, sequestering PRC1 components into complexes that lack the ability to interact efficiently with histones. These findings demonstrate the important role of PCGF2 in human development and confirm that heterozygous substitutions of the Pro65 residue of PCGF2 cause a recognizable syndrome characterized by distinctive craniofacial, neurological, cardiovascular, and skeletal features.
RESUMO
BACKGROUND: The immediate and longer-term effects of hemodialysis on cerebral circulation, cerebral structure, and cognitive function are poorly understood. METHODS: In a prospective observational cohort study of 97 adults (median age 59 years) receiving chronic hemodialysis, we used transcranial Doppler ultrasound to measure cerebral arterial mean flow velocity (MFV) throughout dialysis. Using a well validated neuropsychological protocol, we assessed cognitive function during and off dialysis and after 12 months of treatment. We also used brain magnetic resonance imaging (MRI) to assess atrophy, white matter hyperintensities (WMHs), and diffusion parameters, and tested correlations between MFV, cognitive scores, and changes on MRI. RESULTS: MFV declined significantly during dialysis, correlating with ultrafiltrate volumes. Percentage of decline in MFV correlated with intradialytic decline in cognitive function, including global function, executive function, and verbal fluency. At follow-up, 73 patients were available for repeat testing, 34 of whom underwent repeat MRI. In a subgroup of patients followed for 12 months of continued dialysis, percentage of decline in MFV correlated significantly with lower global and executive function and with progression of WMH burden (a marker of small vessel disease). Twelve of 15 patients who received renal transplants during follow-up had both early and follow-up off-dialysis assessments. After transplant, patients' memory (on a delayed recall test) improved significantly; increased fractional anisotropy of white matter (a measure of cerebral diffusion) in these patients correlated with improving executive function. CONCLUSIONS: Patients undergoing hemodialysis experience transient decline in cerebral blood flow, correlating with intradialytic cognitive dysfunction. Progressive cerebrovascular disease occurred in those continuing dialysis, but not in transplanted patients. Cognitive function and cerebral diffusion improved after transplant.
Assuntos
Circulação Cerebrovascular/fisiologia , Disfunção Cognitiva/epidemiologia , Falência Renal Crônica/terapia , Imageamento por Ressonância Magnética/métodos , Diálise Renal/efeitos adversos , Ultrassonografia Doppler Transcraniana/métodos , Adulto , Fatores Etários , Idoso , Distribuição de Qui-Quadrado , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Estudos de Coortes , Progressão da Doença , Feminino , Seguimentos , Humanos , Incidência , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Diálise Renal/métodos , Medição de Risco , Fatores Sexuais , Estatísticas não Paramétricas , Análise de Sobrevida , Fatores de TempoRESUMO
Copper is an essential trace element that is involved in a number of important enzymatic processes throughout the body. Recent single case reports and small studies have shown that deficiency of copper can cause reversible haematological changes and irreversible neurological injury. We chose to undertake a national study, looking at all cases of copper deficiency in Scotland over a 5-yr period using information from a national reference laboratory. From 16 identified patients, we determined that 86% had both haematological and neurological features of copper deficiency, while 18% had haematological features only at presentation. Twelve of the sixteen patients had high serum zinc concentrations (>18 µm/L) nine patients were using zinc-containing dental fixatives at time of diagnosis. 94% of patients had haematological features as an initial manifestation of copper deficiency, which included anaemia, thrombocytopenia and neutropenia. Patients who underwent later bone marrow testing had appearances in keeping with refractory cytopenia with multilineage dysplasia, refractory anaemia with excess of blasts, unclassified marrow dysplasia or probable myelodysplasia (MDS). 75% of patients had neurological symptoms or signs, including progressive walking difficulties and paraesthesia, or gait difficulties without sensory signs. Clinical examination was in keeping with spastic paraparesis (either with or without sensory neuropathy). Magnetic resonance imaging (MRI) showed multifocal T2 hyper intense foci in the subcortical white matter, and atrophy of the cerebrum and cerebellum was also seen on computerised tomography (CT). MRI of the spinal cord showed signal change in the dorsal columns in either the cervical or thoracic cord. 93% of cytopenias responded to copper replacement and addressing the original cause of the copper deficiency, but only 25% of patients had improvement in their neurological function, while 33% deteriorated and 42% remained unchanged. Our study demonstrates that copper deficiency is an under-recognised cause of several types of cytopenia, which are reversible but can progress to significant neurological injury if left untreated. We illustrate the importance of identifying these patients early to prevent irreversible neurological injury.
Assuntos
Cobre/deficiência , Doenças Hematológicas/complicações , Doenças Hematológicas/diagnóstico , Doenças da Medula Espinal/complicações , Doenças da Medula Espinal/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/complicações , Anemia/diagnóstico , Anemia/tratamento farmacológico , Medula Óssea/patologia , Cobre/sangue , Sulfato de Cobre/uso terapêutico , Feminino , Doenças Hematológicas/tratamento farmacológico , Humanos , Linfopenia/complicações , Linfopenia/diagnóstico , Linfopenia/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neutropenia/complicações , Neutropenia/diagnóstico , Neutropenia/tratamento farmacológico , Pancitopenia/complicações , Pancitopenia/diagnóstico , Pancitopenia/tratamento farmacológico , Estudos Retrospectivos , Escócia , Medula Espinal/patologia , Doenças da Medula Espinal/tratamento farmacológico , Trombocitopenia/complicações , Trombocitopenia/diagnóstico , Trombocitopenia/tratamento farmacológico , Resultado do Tratamento , Adulto Jovem , Zinco/sangue , Zinco/deficiênciaRESUMO
BACKGROUND: Higher field strength magnetic resonance imaging (MRI) is becoming increasingly available and offers improved image quality; however, the clinical usefulness of this technique for the demonstration of surgically treatable functional pituitary adenomas has not been clearly established. OBJECTIVE: To determine whether 3 Tesla (3T) MRI improves the detection of ACTH- and GH-secreting microadenomas over conventional imaging at field strengths of up to 1·5 Tesla (1·5T). DESIGN: Data sets from postgadolinium T1-weighted MRI at 1·5T and 3T were blinded, randomly ordered and assessed for the presence of pituitary tumour by two radiologists. Where possible, lesion signal difference to noise ratio (SDNR) was calculated for quantitative comparison. Imaging diagnoses were correlated with subsequent surgical and histological findings. PATIENTS: Twenty-four patients (10 men, 14 women) with biochemical evidence of Cushing's disease (19) or acromegaly (5) were identified over a 5-year period. RESULTS: 1·5T MRI gave a clear diagnosis of 12 pituitary tumours, all confirmed at 3T. Four additional definite lesions and one suspicious case were correctly identified at 3T. Histological correlation in 21 cases showed sensitivity improving from 54% with 1·5T to 85% with 3T. Radiologists' subjective image preference favoured 3T in 92%. Quantitative difference between tumour and parenchymal signal was significantly greater at 3T (mean SDNR -7·9 [3T] and -2·8 [1·5T], paired t-test P < 0·05). CONCLUSIONS: 3T MRI appears to offer increased conspicuity and detection of GH- and ACTH-secreting pituitary microadenomas. It is potentially clinically useful when 1·5T imaging is negative or equivocal.
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Imageamento por Ressonância Magnética/métodos , Neoplasias Hipofisárias/patologia , Acromegalia/metabolismo , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Feminino , Hormônio do Crescimento/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Hipersecreção Hipofisária de ACTH/metabolismo , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/metabolismo , RadiografiaRESUMO
BACKGROUND AND PURPOSE: Periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER or PROP) is an effective means of compensating for head motion during MR imaging in adults. The aim of this study was to assess the value of this novel technique in unsedated children. METHODS: PROP T2-weighted fast spin-echo (FSE) imaging (TR/TE/NEX, 4000/83/2; 50 seconds) and T2-weighted single-shot FSE (SS-FSE) imaging (19,929/92/0.5; imaging time, 25 seconds) were performed in 35 unsedated children (mean age, 4.7 years +/- 4.2) who were undergoing brain MR imaging. Two observers assessed unlabelled images for motion artifact, other artifacts, visibility of pathology, and the preferred image overall. Sequences were compared by using the chi(2) test and concordant data from both observers. RESULTS: Both PROP and the SS-FSE imaging offered equal degrees of motion correction. Metallic artifacts were worse on PROP imaging, likely because of a higher receiver bandwidth (P <.001, chi(2) test). Pathology was present in 28 subjects and equally well seen on PROP and SS-FSE images. Overall, PROP was preferred, largely because of its improvements in image contrast (P <.001, chi(2) test). CONCLUSION: SS-FSE imaging and PROP provide equal motion correction, although PROP enables better assessment of the brain parenchyma.
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Encéfalo/patologia , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Adolescente , Artefatos , Criança , Pré-Escolar , Sedação Consciente , Movimentos da Cabeça , Humanos , Lactente , Recém-Nascido , Variações Dependentes do ObservadorRESUMO
BACKGROUND AND PURPOSE: The aim of this study was to assess the effect of zero-filled interpolation (ZIP) on measurements of the cervical arteries because its benefits on the accuracy and precision of measurements in medium-sized arteries remains unknown. METHODS: Three observers measured 36 computer-simulated vessels (2-6.8 mm) and 130 normal cervical vessels (assessed with two-dimensional time-of-flight MR angiography) from 512-, 256-, and 256-ZIP matrix source images. The accuracy and precision of measurement was assessed for each matrix by using the Student t test and F test of variance, respectively. The effect of vessel size and matrix placement on measurement error was determined by means of linear regression and the Student t test, respectively. RESULTS: No significant difference was observed between simulated measurements obtained on the 512 matrix and their true value. The 256 matrix caused overestimation of vessel diameter compared with 512 matrix (mean bias, 0.3 mm for computer-simulated vessels and 0.1 mm for normal vessels). This effect was reduced with ZIP, by a mean of 0.1 mm for both groups (P <.03). Precision was not affected by the matrix size or ZIP, and vessel size and matrix placement did not alter the measurement error. CONCLUSION: Vessel diameter is overestimated on 256-matrix MR angiographic source images. ZIP reduces this overestimation; however, the effect is small and unlikely to be clinically important.
Assuntos
Simulação por Computador , Angiografia por Ressonância Magnética/estatística & dados numéricos , Modelos Cardiovasculares , Pescoço/irrigação sanguínea , Artérias/patologia , Viés , Humanos , Modelos Lineares , Computação Matemática , Valores de ReferênciaRESUMO
Over the last 20 years there have been great advances in the field of neuroimaging. However, information is still lacking for patients with a disorder of sex development (DSD) due to the rarity of these conditions. In this chapter the authors will review newly emerging techniques with a focus on the connectivity of the brain, describe sexually dimorphic brain structures and functions, and summarise what is known about the neuroanatomy and neurochemistry of individuals with a DSD. Sexual dimorphism exists in all aspects of neuroanatomy, neurochemistry and neurofunction, but the major challenge is to evaluate the relationship between these differences and relate them to the genetic and hormonal environment of the individual. Further imaging studies of normal gender differences are needed before the implications of neuroimaging findings for individuals with a DSD can be determined. Future directions for study include the association between gender-specific brain connectivity patterns and gender-related differences of various brain diseases.
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Encéfalo/patologia , Transtornos do Desenvolvimento Sexual/patologia , Neuroimagem/métodos , Caracteres Sexuais , Encéfalo/fisiopatologia , Transtornos do Desenvolvimento Sexual/fisiopatologia , Feminino , Humanos , Masculino , Neuroimagem/tendênciasRESUMO
BACKGROUND: The potential morbidity of cerebral ischemia after carotid endarterectomy (CEA) has been recognized, but its reported incidence varies widely. OBJECTIVE: To prospectively evaluate the development of cerebral ischemic complications in patients treated by CEA at a high-volume cerebrovascular center. METHODS: Fifty patients with moderate or severe carotid stenosis awaiting CEA were studied with perioperative diffusion-weighted imaging of the brain and standardized neurological evaluations. Microsurgical CEA was performed by 1 of 2 vascular neurosurgeons. Radiological studies were evaluated by faculty neuroradiologists who were blinded to the details of the clinical situation. RESULTS: Preoperative diffusion-weighted imaging studies were performed within 24 hours of surgery. A second study was obtained within 24 (92% of patients), 48 (4% of patients), or 72 (4% of patients) hours after surgery. Intraluminal shunting was used in 1 patient (2%), and patch angioplasty was used in 2 patients (4%). No patient had diffusion-weighted imaging evidence of procedure-related cerebral ischemia. Nonischemic complications consisted of postoperative confusion in an 87-year-old man with a urinary tract infection and a marginal mandibular nerve paresis in another patient. Radiological studies were normal in both patients. CONCLUSION: CEA is a relatively safe procedure that may be performed with an acceptable risk of cerebral ischemia in select patients. The low rate of ischemic complications associated with CEA sets a standard to which other carotid revascularization techniques should be held. The current results are presented with a discussion of the senior author's preferred surgical technique and a brief review of the literature.
Assuntos
Isquemia Encefálica/etiologia , Isquemia Encefálica/patologia , Endarterectomia das Carótidas , Complicações Pós-Operatórias/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/complicações , Aterosclerose/patologia , Isquemia Encefálica/epidemiologia , Estenose das Carótidas/patologia , Estenose das Carótidas/cirurgia , Angiografia Cerebral , Imagem de Difusão por Ressonância Magnética , Endarterectomia das Carótidas/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Perioperatório , Fatores de Risco , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
A method for obtaining diffusion-weighted images that are free from the artifacts associated with echo-planar acquisitions, such as signal pile-up and geometric warping, is introduced. It uses an ungated, multishot fast spin-echo (FSE) acquisition that is self-navigated. The phase of the refocusing pulses is alternated to minimize non-Carr-Purcell-Meiboom-Gill (CPMG) artifacts. Several reconstruction methods are combined to make this method robust against motion artifacts. Examples are shown of clinical diffusion-weighted imaging and high-resolution diffusion tensor imaging.
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Artefatos , Encéfalo/patologia , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Algoritmos , HumanosRESUMO
PURPOSE: To evaluate the normal water diffusion changes that occur during the 1st year of life. MATERIALS AND METHODS: Diffusion-weighted imaging was performed in 40 subjects (age range, birth to 1 year) in whom both magnetic resonance imaging and neurologic assessment results were normal at the time of imaging and, where available, at follow-up. Apparent diffusion coefficient (ADC) was calculated in four areas of white matter (anterior and posterior subcortical and internal capsule) and four of gray matter (cortex, thalamus, head of the caudate nucleus, and lentiform nucleus). Linear regression was used to examine the effect of age on ADC, and analysis of variance was used to compare ADC within different brain regions. RESULTS: ADC decreased with age in all regions (P <.01). Data best fit with a logarithmic decline (r(2) = 0.20-0.63). ADC was significantly higher in white (113 x 10(-5) mm(2)/sec) than in gray matter (102 x 10(-5) mm(2)/sec; P <.001). Significant differences were seen among three white matter regions (subcortical, 188 x 10(-5) mm(2)/sec at birth; anterior limb of internal capsule, 130 x 10(-5) mm(2)/sec; posterior limb of internal capsule, 109 x 10(-5) mm(2)/sec) and three gray matter regions (cortex, 134 x 10(-5) mm(2)/sec at birth; head of caudate nucleus, 134 x 10(-5) mm(2)/sec at birth; and thalamus and lentiform nucleus, 120 x 10(-5) mm(2)/sec; P <.01). CONCLUSION: Results suggest that in neonates and infants, water diffusion is highly dependent on both subject age and brain location.
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Encéfalo/metabolismo , Água/metabolismo , Fatores Etários , Feminino , Humanos , Lactente , Recém-Nascido , MasculinoRESUMO
PURPOSE: To compare periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) multishot fast spin-echo diffusion-weighted magnetic resonance (MR) imaging with single-shot echo-planar diffusion-weighted MR imaging for image quality and visualization of acute cerebral infarction. MATERIALS AND METHODS: Seventy subjects (35 men, 35 women; mean age, 55 years +/- 24 [SD]) who were suspected of having acute cerebral infarction (symptom duration, 2.8 days +/- 2.7) underwent PROPELLER and echo-planar MR imaging (b = 1,000 sec/mm(2)). Two neuroradiologists compared unlabeled images for presence of artifacts, visualization of infarction, and their preference of images. Interobserver agreement and image comparison were assessed by using the kappa statistic and the chi(2) test, respectively. RESULTS: PROPELLER MR imaging reduced susceptibility artifacts (n = 70 subjects), which limited visualization of temporal (echo-planar, n = 64; PROPELLER, n = 0; P <.01, chi(2) test), frontal (echo-planar, n = 58; PROPELLER, n = 1; P <.01), and parietal lobes (echo-planar, n = 5; PROPELLER, n = 0; P <.05) and cerebellum (echo-planar, n = 36; PROPELLER, n = 0; P <.01) and brainstem (echo-planar, n = 23; PROPELLER, n = 0; P <.01). Acute infarction (n = 31 subjects) was better demonstrated at PROPELLER MR imaging (PROPELLER better, n = 18; echo-planar better, n = 1; PROPELLER and echo-planar equal, n = 12; P <.01, chi(2) test). PROPELLER MR imaging was preferred in all (n = 70) but one case in which the lesion lay within the intersection gap (PROPELLER preferred, n = 69; echo-planar preferred, n = 1; P <.01, chi(2) test). CONCLUSION: With a short increase in imaging time, PROPELLER MR imaging offers better image quality and detection of acute cerebral infarction than does echo-planar MR imaging.