RESUMO
BACKGROUND: The brain functional correlates of autobiographical recall are well established, but have been little studied in schizophrenia. Additionally, autobiographical memory is one of a small number of cognitive tasks that activates rather than de-activates the default mode network, which has been found to be dysfunctional in this disorder. METHODS: Twenty-seven schizophrenic patients and 30 healthy controls underwent functional magnetic resonance imaging while viewing cue words that evoked autobiographical memories. Control conditions included both non-memory-evoking cues and a low level baseline (cross fixation). RESULTS: Compared to both non-memory evoking cues and low level baseline, autobiographical recall was associated with activation in default mode network regions in the controls including the medial frontal cortex, the posterior cingulate cortex and the hippocampus, as well as other areas. Clusters of de-activation were seen outside the default mode network. There were no activation differences between the schizophrenic patients and the controls, but the patients showed clusters of failure of de-activation in non-default mode network regions. CONCLUSIONS: According to this study, patients with schizophrenia show intact activation of the default mode network and other regions associated with recall of autobiographical memories. The finding of failure of de-activation outside the network suggests that schizophrenia may be associated with a general difficulty in de-activation rather than dysfunction of the default mode network per se.
Assuntos
Rede de Modo Padrão/fisiopatologia , Memória Episódica , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Adulto , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: An alteration in self/other differentiation has been proposed as a basis for several symptoms in schizophrenia, including delusions of reference and social functioning deficits. Dysfunction of the right temporo-parietal junction (TPJ), a region linked with social cognition, has been proposed as the basis of this alteration. However, imaging studies of self- and other-processing in schizophrenia have shown, so far, inconsistent results. METHODS: Patients with schizophrenia and healthy controls underwent fMRI scanning while performing a task with three conditions: self-reflection, other-reflection and semantic processing. RESULTS: Both groups activated similar brain regions for self- and other-reflection compared to semantic processing, including the medial prefrontal cortex, the precuneus and the TPJ. Compared to healthy subjects, patients hyperactivated the left lateral frontal cortex during self- and other-reflection. In other-reflection, compared to self-reflection, patients failed to increase right TPJ activity. CONCLUSIONS: Altered activity in the right TPJ supports a disturbance in self/other differentiation in schizophrenia, which could be linked with psychotic symptoms and affect social functioning in patients. Hyperactivity of the lateral frontal cortex for self- and other-reflection suggests the presence of greater cognitive demand to perform the task in the patient group.
Assuntos
Encéfalo/fisiopatologia , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Autoimagem , Cognição Social , Teoria da Mente/fisiologia , Adulto JovemRESUMO
The default-mode network (DMN) comprises a set of brain regions that show deactivations during performance of attentionally demanding tasks, but also activation during certain processes including recall of autobiographical memories and processing information about oneself, among others. However, the DMN is not activated in a homogeneous manner during performance of such tasks, so it is not clear to what extent its activation patterns correspond to deactivation patterns seen during attention-demanding tasks. In this fMRI study we compared patterns of activation in response to an autobiographical memory task to those observed in a self/other-reflection task, and compared both to deactivations observed during the n-back working memory task. Autobiographical recall and self-reflection activated several common DMN areas, which were also deactivated below baseline levels by the n-back task. Activation in the medial temporal lobe was seen during autobiographical recall but not the self/other task, and right angular gyrus activity was specifically linked to other-reflection. ROI analysis showed that most, but not all DMN regions were activated above baseline levels during the autobiographical memory and self-reflection tasks. Our results provide evidence for the usefulness of the autobiographical memory task to study DMN activity and support the notion of interacting subsystems within this network.
Assuntos
Atenção/fisiologia , Encéfalo/fisiologia , Memória Episódica , Adolescente , Adulto , Idoso , Encéfalo/anatomia & histologia , Mapeamento Encefálico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Memória de Curto Prazo/fisiologia , Rememoração Mental/fisiologia , Pessoa de Meia-Idade , Rede Nervosa/fisiologia , Vias Neurais/fisiologia , Autoavaliação (Psicologia) , Análise e Desempenho de Tarefas , Adulto JovemRESUMO
Aims: P2Y12 antagonists are the standard in antiplatelet therapy but their potential effects on functional myocardial recovery and cardioprotection post-myocardial infarction (MI) are unknown. We investigated in a preclinical model of MI whether ticagrelor and clopidogrel differently affect cardiac repair post-MI. Methods and results: Pigs either received: (i) clopidogrel (600 mg; 75 mg/qd); (ii) ticagrelor (180 mg; 90 mg/bid); and (iii) placebo control. MI was induced by mid-left anterior descending coronary artery balloon occlusion (60 min) and animals received the maintenance doses for the following 42 days. Serial cardiac magnetic resonance was performed at Day 3 and Day 42 for the assessment of global and regional cardiac parameters. We determined cardiac AMP-activated protein kinase (AMPK), Akt/PKB, aquaporin-4, vascular density, and fibrosis. In comparison to controls, both P2Y12 antagonists limited infarct expansion at Day 3, although ticagrelor induced a further 5% reduction (P < 0.05 vs. clopidogrel) whereas oedema was only reduced by ticagrelor (≈23% P < 0.05). Scar size decreased at Day 42 in ticagrelor-treated pigs vs. controls but not in clopidogrel-treated pigs. Left ventricular ejection fraction was higher 3 days post-MI in ticagrelor-treated pigs and persisted up to Day 42 (P < 0.05 vs. post-MI). Regional analysis revealed that control and clopidogrel-treated pigs had severe and extensive wall motion abnormalities in the jeopardized myocardium and a reduced myocardial viability that was not as evident in ticagrelor-treated pigs (χ2P < 0.05 vs. ticagrelor). Only ticagrelor enhanced myocardial AMPK and Akt/PKB activation and reduced aquaporin-4 levels (P < 0.05 vs. control and clopidogrel). No differences were observed in vessel density and fibrosis markers among groups. Conclusions: Ticagrelor is more efficient than clopidogrel in attenuating myocardial structural and functional alterations post-MI and in improving cardiac healing. These benefits are associated with persistent AMPK and Akt/PKB activation.
Assuntos
Clopidogrel/farmacologia , Ventrículos do Coração/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Receptores Purinérgicos P2/efeitos dos fármacos , Ticagrelor/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Modelos Animais de Doenças , Ecocardiografia , Fibrose , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/metabolismo , Ventrículos do Coração/fisiopatologia , Imagem Cinética por Ressonância Magnética , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Purinérgicos P2/metabolismo , Receptores Purinérgicos P2Y12 , Transdução de Sinais/efeitos dos fármacos , Volume Sistólico/efeitos dos fármacos , Sus scrofa , Fatores de Tempo , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacosRESUMO
BACKGROUND: Myocardial microvascular loss after myocardial infarction (MI) remains a therapeutic challenge. Autologous stem cell therapy was considered as an alternative; however, it has shown modest benefits due to the impairing effects of cardiovascular risk factors on stem cells. Allogenic adipose-derived stem cells (ASCs) may overcome such limitations, and because of their low immunogenicity and paracrine potential may be good candidates for cell therapy. In the present study we investigated the effects of allogenic ASCs and their released products on cardiac rarefaction post MI. METHODS: Pig subcutaneous adipose tissue ASCs were isolated, expanded and GFP-labeled. ASC angiogenic function was assessed by the in-vivo chick chorioallantoic membrane (CAM) model. Pigs underwent MI induction and 7 days after were randomized to receive: allogenic ASCs (intracoronary infusion); conditioned media (CM; intravenous infusion); ASCs + CM; or PBS/placebo (control). Cardiac damage and function were monitored by 3-T cardiac magnetic resonance imaging upon infusion (baseline CMR) and 1 and 3 weeks thereafter. We assessed in the myocardium: microvessel density; angiogenic markers (CD105, CD31, TF, VEGFR2, VEGFR1, vWF, eNOS, CD62); collagen deposition; and reparative fibrosis (TGFß/TßRII/collagen). Differential proteomics of ASCs and CM was performed to characterize the ASC protein signature. RESULTS: CAM indicated a significant ASC proangiogenic capacity. In pigs after MI, only PBS/placebo animals displayed an impaired cardiac function 3 weeks after infusion (p < 0.05 vs baseline). Administration of ASCs + CM significantly enhanced neovessel formation and favored cardiac repair post MI (p < 0.05 vs the other groups). Molecular markers of angiogenesis were significantly upregulated both at transcriptional and protein levels (p < 0.05). The in-silico bioinformatics analysis of the ASC and CM proteome (interactome) indicated activation of a coordinated protein network involved in the formation of microvessels and the resolution of rarefaction. CONCLUSION: Coadministration of allogenic ASCs and their CM synergistically contribute to the neovascularization of the infarcted myocardium through a coordinated upregulation of the proangiogenic protein interactome.
Assuntos
Infarto do Miocárdio/terapia , Isquemia Miocárdica/terapia , Transplante de Células-Tronco , Transplante Autólogo , Tecido Adiposo/citologia , Animais , Terapia Baseada em Transplante de Células e Tecidos , Humanos , Microvasos/crescimento & desenvolvimento , Microvasos/fisiopatologia , Infarto do Miocárdio/fisiopatologia , Isquemia Miocárdica/fisiopatologia , Miocárdio/patologia , Fatores de Risco , Suínos , Biologia de SistemasRESUMO
BACKGROUND: The P2Y12 receptor antagonist ticagrelor has been shown to be clinically superior to clopidogrel. Although the underlying mechanisms remain elusive, ticagrelor may exert off-target effects through adenosine-related mechanisms. We aimed to investigate whether ticagrelor reduces myocardial injury to a greater extent than clopidogrel after myocardial infarction (MI) at a similar level of platelet inhibition and to determine the underlying mechanisms. METHODS: Pigs received the following before MI induction: (1) placebo-control; (2) a loading dose of clopidogrel (600 mg); (3) a loading dose of ticagrelor (180 mg); or (4) a loading dose of ticagrelor followed by an adenosine A1/A2-receptor antagonist [8-(p-sulfophenyl)theophylline, 4 mg/kg intravenous] to determine the potential contribution of adenosine in ticagrelor-related cardioprotection. Animals received the corresponding maintenance doses of the antiplatelet agents during the following 24 hours and underwent 3T-cardiac MRI analysis. Platelet inhibition was monitored by ADP-induced platelet aggregation. In the myocardium, we assessed the expression and activation of proteins known to modulate edema formation, including aquaporin-4 and AMP-activated protein kinase and its downstream effectors CD36 and endothelial nitric oxide synthase and cyclooxygenase-2 activity. RESULTS: Clopidogrel and ticagrelor exerted a high and consistent antiplatelet effect (68.2% and 62.2% of platelet inhibition, respectively, on challenge with 20 µmol/L ADP) that persisted up to 24 hours post-MI (P<0.05). All groups showed comparable myocardial area-at-risk and cardiac worsening after MI induction. 3T-Cardiac MRI analysis revealed that clopidogrel- and ticagrelor-treated animals had a significantly smaller extent of MI than placebo-control animals (15.7 g left ventricle and 12.0 g left ventricle versus 22.8 g left ventricle, respectively). Yet, ticagrelor reduced infarct size to a significantly greater extent than clopidogrel (further 23.5% reduction; P=0.0026), an effect supported by troponin-I assessment and histopathologic analysis (P=0.0021). Furthermore, in comparison with clopidogrel, ticagrelor significantly diminished myocardial edema by 24.5% (P=0.004), which correlated with infarct mass (r=0.73; P<0.001). 8-(p-Sulfophenyl)theophylline administration abolished the cardioprotective effects of ticagrelor over clopidogrel. At a molecular level, aquaporin-4 expression decreased and the expression and activation of AMP-activated protein kinase signaling and cyclooxygenase-2 increased in the ischemic myocardium of ticagrelor- versus clopidogrel-treated animals (P<0.05). These protein changes were not observed in those animals administered the adenosine receptor blocker 8-(p-sulfophenyl)theophylline. CONCLUSIONS: Ticagrelor, beyond its antiplatelet efficacy, exerts cardioprotective effects by reducing necrotic injury and edema formation via adenosine-dependent mechanisms.
Assuntos
Adenosina/análogos & derivados , Cardiotônicos/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Ticlopidina/análogos & derivados , Adenosina/farmacologia , Animais , Plaquetas/efeitos dos fármacos , Clopidogrel , Ciclo-Oxigenase 2/metabolismo , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/patologia , Inibidores da Agregação Plaquetária/farmacologia , Distribuição Aleatória , Suínos , Ticagrelor , Ticlopidina/farmacologiaRESUMO
BACKGROUND: Although there are undeniable diagnostic benefits of CT scanning, its increasing use in paediatric radiology has become a topic of concern regarding patient radioprotection. OBJECTIVE: To assess the rate of CT scanning in Catalonia, Spain, among patients younger than 21 years old at the scan time. MATERIALS AND METHODS: This is a sub-study of a larger international cohort study (EPI-CT, the International pediatric CT scan study). Data were retrieved from the radiological information systems (RIS) of eight hospitals in Catalonia since the implementation of digital registration (between 1991 and 2010) until 2013. RESULTS: The absolute number of CT scans annually increased 4.5% between 1991 and 2013, which was less accentuated when RIS was implemented in most hospitals. Because the population attending the hospitals also increased, however, the rate of scanned patients changed little (8.3 to 9.4 per 1,000 population). The proportions of patients with more than one CT and more than three CTs showed a 1.51- and 2.7-fold increase, respectively, over the 23 years. CONCLUSION: Gradual increases in numbers of examinations and scanned patients were observed in Catalonia, potentially explained by new CT scanning indications and increases in the availability of scanners, the number of scans per patient and the size of the attended population.
Assuntos
Padrões de Prática Médica/estatística & dados numéricos , Padrões de Prática Médica/tendências , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Tomografia Computadorizada por Raios X/tendências , Adolescente , Adulto , Distribuição por Idade , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Espanha/epidemiologia , Adulto JovemAssuntos
Colesterol na Dieta/efeitos adversos , Hipercolesterolemia/sangue , Hipercolesterolemia/induzido quimicamente , Lipoproteínas HDL/sangue , Infarto do Miocárdio/sangue , Infarto do Miocárdio/prevenção & controle , Animais , Colesterol na Dieta/administração & dosagem , Hipercolesterolemia/complicações , Lipoproteínas HDL/administração & dosagem , SuínosRESUMO
PURPOSE: The aim of this study was to apply sequential analysis of electroencephalography-functional magnetic resonance imaging (EEG-fMRI) data to study the cortical substrates related to the generation of the interictal epileptiform activity (IEA) in patients with pharmacoresistant extratemporal epilepsy. METHODS: We analyzed fMRI data from 21 children, adolescents, and young adults patients who showed frequent bursts or runs of spikes on EEG, by using the sequential analysis method. We contrasted consecutive fixed-width blocks of 10 s to obtain the relative variations in cerebral activity along the entire fMRI runs. Significant responses (p < 0.05, family-wise error (FWE) corrected), time-related to the IEA recorded on scalp EEG, were considered potential IEA cortical sources. These results were compared with those from the fluorodeoxyglucose-positron emission tomography (FDG-PET), intracranial EEG (two patients), and surgery outcome (eight patients). KEY FINDINGS: The typical IEA was recorded in all patients. After the sequential analysis, at least one significant blood oxygen level-dependent (BOLD) response spatially consistent with the presumed epileptogenic zone was found. These IEA-related activation areas coincided when superimposed with the hypometabolism depicted by the FDG-PET. These data were also consistent with the invasive EEG findings. Epileptic seizures were recorded in eight patients. A subset of IEA-associated fMRI activations was consistent the activations at seizure-onset determined by sequential analysis. The inclusion of the IEA-related areas in the resection rendered the patients seizure-free (five of eight operated patients). SIGNIFICANCE: The EEG-fMRI data sequential analysis could noninvasively identify cortical areas involved in the IEA generation. The spatial relationship of these areas with the cortical metabolic abnormalities depicted by the FDG-PET and their intrinsic relationship regarding the ictal-onset zone could be useful in epilepsy surgery planning.
Assuntos
Córtex Cerebral/fisiopatologia , Epilepsia/diagnóstico , Epilepsia/fisiopatologia , Adolescente , Adulto , Anticonvulsivantes/uso terapêutico , Criança , Pré-Escolar , Eletroencefalografia , Feminino , Fluordesoxiglucose F18 , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Oxigênio/sangue , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: Manic patients have been found to show reduced activation in the prefrontal cortex and other regions during performance of cognitive tasks. However, little is known about de-activations associated with the disorder. This study aimed to examine, at the whole-brain level, abnormal patterns of task-related activation and de-activation during performance of a working memory task. METHODS: Twenty-nine DSM-IV bipolar patients and 46 healthy controls underwent fMRI during performance of the n-back task. The patients were scanned while they were in a manic episode. Linear models were used to obtain maps of within-group activations and areas of differential activation between the groups. RESULTS: The manic patients showed reduced activation compared to the controls in the bilateral dorsolateral prefrontal cortex and the right parietal cortex. They also showed failure of de-activation in the medial frontal cortex, extending to the temporal poles and parts of the limbic system bilaterally. The failure of activation in the dorsolateral prefrontal cortex disappeared when differences in task performance were controlled for in the analysis. However, the medial frontal failure of de-activation survived controlling for this. CONCLUSIONS: This study suggests that, in addition to reduced prefrontal activation, failure of de-activation is an important functional imaging abnormality in mania. This, together with its location in the medial prefrontal cortex, implies default mode network dysfunction in the disorder.
Assuntos
Transtorno Bipolar/fisiopatologia , Rede Nervosa/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Adulto , Discriminação Psicológica/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética/instrumentação , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Adulto JovemRESUMO
BACKGROUND: Cognitive impairment is an established feature of schizophrenia. However, little is known about its relationship to the structural and functional brain abnormalities that characterise the disorder. Aims To identify structural and/or functional brain abnormalities associated with schizophrenic cognitive impairment. METHOD: We carried out structural magnetic resonance imaging (MRI) and voxel-based morphometry in 26 participants who were cognitively impaired and 23 who were cognitively preserved, all with schizophrenia, plus 39 matched controls. Nineteen of those who were cognitively impaired and 18 of those who were cognitively preserved plus 34 controls also underwent functional MRI during performance of a working memory task. RESULTS: No differences were found between the participants who were cognitively intact and those who were cognitively impaired in lateral ventricular volume or whole brain volume. Voxel-based morphometry also failed to reveal clusters of significant difference in grey and white matter volume between these two groups. However, during performance of the n-back task, the participants who were cognitively impaired showed hypoactivation compared with those who were cognitively intact in the dorsolateral prefrontal cortex among other brain regions. CONCLUSIONS: Cognitive impairment in schizophrenia is not a function of the structural brain abnormality that accompanies the disorder but has correlates in altered brain function.
Assuntos
Encéfalo/patologia , Transtornos Cognitivos/patologia , Esquizofrenia/patologia , Psicologia do Esquizofrênico , Adulto , Encéfalo/anormalidades , Encéfalo/fisiopatologia , Mapeamento Encefálico , Estudos de Casos e Controles , Transtornos Cognitivos/fisiopatologia , Feminino , Lateralidade Funcional , Humanos , Processamento de Imagem Assistida por Computador/métodos , Ventrículos Laterais/patologia , Imageamento por Ressonância Magnética/métodos , Masculino , Memória de Curto Prazo/fisiologia , Testes Neuropsicológicos , Córtex Pré-Frontal/fisiopatologia , Esquizofrenia/fisiopatologiaRESUMO
OBJECT: This study demonstrates that 3T SV-MRS data can be used with the currently available automatic brain tumour diagnostic classifiers which were trained on databases of 1.5T spectra. This will allow the existing large databases of 1.5T MRS data to be used for diagnostic classification of 3T spectra, and perhaps also the combination of 1.5T and 3T databases. MATERIALS AND METHODS: Brain tumour classifiers trained with 154 1.5T spectra to discriminate among high grade malignant tumours and common grade II glial tumours were evaluated with a subsequently-acquired set of 155 1.5T and 37 3T spectra. A similarity study between spectra and main brain tumour metabolite ratios for both field strengths (1.5T and 3T) was also performed. RESULTS: Our results showed that classifiers trained with 1.5T samples had similar accuracy for both test datasets (0.87 ± 0.03 for 1.5T and 0.88 ± 0.03 for 3.0T). Moreover, non-significant differences were observed with most metabolite ratios and spectral patterns. CONCLUSION: These results encourage the use of existing classifiers based on 1.5T datasets for diagnosis with 3T (1)H SV-MRS. The large 1.5T databases compiled throughout many years and the prediction models based on 1.5T acquisitions can therefore continue to be used with data from the new 3T instruments.
Assuntos
Neoplasias Encefálicas/diagnóstico , Bases de Dados Factuais , Espectroscopia de Ressonância Magnética/métodos , Reconhecimento Automatizado de Padrão/métodos , Neoplasias Encefálicas/metabolismo , Humanos , Prótons , Sensibilidade e EspecificidadeRESUMO
Iron chelators are a new therapeutical approach for patients with Friedreich's ataxia, on the basis that oxidative cell damage that occurs in these patients is due to the increasing deposits of mitochondrial iron pools. The objective of the study was to evaluate the effects of the combined therapy of idebenone and low oral doses of deferiprone on the neurological signs and cardiac function parameters. This study was designed as a prospective open-label single-arm study. Twenty Friedreich's ataxia patients were treated with idebenone (20 mg/kg/day) and deferiprone (20 mg/kg/day) for 11 months. Patients were evaluated before the start and throughout the study with the International Cooperative Ataxia Rating Scale (ICARS) scores, echocardiographic measurements and MRI (magnetic resonance imaging) techniques to asses brain iron deposits in the dentate nucleus. No significant differences were observed in total ICARS scores when comparing baseline status and the end of the study in the whole group of patients. Posture and gait scores increased significantly after 11 months of therapy (Wilcoxon's test, p = 0.04) and kinetic function improved significantly (Wilcoxon's test, p = 0.015). Echocardiography data showed a significant reduction of the interventricular septum thickness (Wilcoxon's test, p = 0.04) and in the left ventricular mass index (Wilcoxon's test, p = 0.038) after the start of the therapy. The MRI values in the dentate nucleus showed a statistically significant reduction (Wilcoxon's test p = 0.007) between baseline conditions and after 11 months of the therapy. Combined therapy with idebenone and deferiprone in patients with FDRA indicates a stabilizing effect in neurologic dysfunctions due to an improvement in the kinetic functions, with a worsening of gait and posture scores. Heart hypertrophy parameters and iron deposits in dentate nucleus improved significantly. Combined therapy was well tolerated with mild side effects, apart from the risk of neutropenia and progressive reduction of plasma iron parameters.
Assuntos
Antioxidantes/uso terapêutico , Ataxia de Friedreich/tratamento farmacológico , Quelantes de Ferro/uso terapêutico , Piridonas/uso terapêutico , Ubiquinona/análogos & derivados , Adolescente , Adulto , Antioxidantes/efeitos adversos , Contagem de Células Sanguíneas , Química Encefálica/efeitos dos fármacos , Criança , Deferiprona , Quimioterapia Combinada , Disartria/etiologia , Disartria/fisiopatologia , Feminino , Ataxia de Friedreich/diagnóstico por imagem , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Testes de Função Cardíaca , Humanos , Ferro/metabolismo , Quelantes de Ferro/efeitos adversos , Imageamento por Ressonância Magnética , Masculino , Exame Neurológico , Músculos Oculomotores/fisiopatologia , Estudos Prospectivos , Piridonas/efeitos adversos , Distúrbios da Fala/etiologia , Distúrbios da Fala/fisiopatologia , Ubiquinona/efeitos adversos , Ubiquinona/uso terapêutico , Ultrassonografia , Adulto JovemRESUMO
Abnormal interactions between areas of the brain have been pointed as possible causes for schizophrenia. However, the nature of these disturbances and the anatomical location of the regions involved are still unclear. Here, we describe a method to estimate maps of net levels of connectivity in the resting brain, and we apply it to look for differential patterns of connectivity in schizophrenia. This method uses partial coherences as a basic measure of covariability, and it minimises the effect of major physiological noise. When overall (net) connectivity maps of a sample of 40 patients with schizophrenia were compared with the maps from a matched sample of 40 controls, a single area of abnormality was found. It is an area of patient hyper-connectivity and is located frontally, in medial and orbital structures, clearly overlapping the anterior node of the default mode network (DMN). When this area is used as a region of interest in a second-level analysis, it shows functional hyper-connections with several cortical and subcortical structures. Interestingly, the most significant abnormality is found with the caudate, which has a bilateral pattern of abnormality, pointing to a possible DMN-striatum deviant relation in schizophrenia. However, hyper-connectivity observed with other regions (right hippocampus and amygdala, and other cortical structures) suggests a more pervasive alteration of brain connectivity in this disease.
Assuntos
Encéfalo/fisiopatologia , Córtex Cerebral/fisiopatologia , Rede Nervosa/fisiopatologia , Vias Neurais/fisiopatologia , Esquizofrenia/fisiopatologia , Adulto , Encéfalo/anatomia & histologia , Encéfalo/metabolismo , Córtex Cerebral/anatomia & histologia , Córtex Cerebral/metabolismo , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/anatomia & histologia , Rede Nervosa/metabolismo , Vias Neurais/anatomia & histologia , Vias Neurais/metabolismo , Esquizofrenia/diagnóstico , Esquizofrenia/metabolismoRESUMO
BACKGROUND AND OBJECTIVE: Brain creatine (Cr) deficiencies are a group of inborn errors of metabolism that are characterized by an absence or severe reduction of brain Cr. Clinically, these patients can display psychomotor/mental retardation and language disorders, commonly associated with epilepsy or movement disorders. Three metabolic defects are known: two affect synthesis - guanidinoacetate metiltransferase (GAMT) and glycine amidinotransferase (AGAT) deficiencies- and one affect the Cr transporter (CRTR). We present the first three Spanish patients with GAMT deficiency, and we compare their clinical phenotype and treatment response with other published cases. PATIENTS AND METHOD: The three patients presented mental retardation, epilepsy and autistic behaviour. Patient 1 also had severe chorea. Diagnosis was done by biochemical and genetic procedures (guanidinoacetate quantification, determination of GAMT activity and mutation analysis in the GAMT gene). RESULTS: An increase of guanidinoacetate was detected in urine and plasma. Brain magnetic resonance spectroscopy revealed low Cr levels. Enzymatic studies revealed a decreased GAMT activity in fibroblasts. Molecular analysis detected pathogenic mutations in the GAMT gene. After the deficiency was confirmed, the patients started treatment with Cr. In addition, patient 2 and 3 received an arginine-restricted diet and ornithine supplements. All them showed a partial improvement. CONCLUSIONS: Patients with GAMT deficiency have an unspecific but relatively constant clinical presentation. Brain Cr deficiency should be considered in patients with mental retardation of unknown aetiology, specially in those with movement disorders or epilepsy. Early diagnosis is important in cases with known treatment such as GAMT deficiency.
Assuntos
Encefalopatias Metabólicas/genética , Creatina/deficiência , Guanidinoacetato N-Metiltransferase/genética , Mutação , Adolescente , Encefalopatias Metabólicas/diagnóstico , Encefalopatias Metabólicas/tratamento farmacológico , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , EspanhaRESUMO
BACKGROUND: Acute striatal necrosis is a devastating consequence of encephalopathic crisis in patients with glutaric aciduria type I (GA-I), but the mechanisms underlying brain injury are not completely understood. OBJECTIVE: To approach pathophysiological aspects of brain injury in GA-I by means of functional techniques in magnetic resonance imaging (MRI). PATIENTS AND METHODS: Four patients during an acute encephalopathic crisis and three asymptomatic siblings with GA-I underwent single-voxel hydrogen magnetic resonance spectroscopy (MRS) and brain MRI including gradient echo T1-weighted, FLAIR, T2-weighted and diffusion-weighted imaging. RESULTS: The study was performed between three and eight days after the onset of acute encephalopathic crisis. Isotropic diffusion images showed high signal changes with corresponding low apparent diffusion coefficient values within the putamen, caudate nuclei and globus pallidus (four patients), and the cerebral peduncles including the substantia nigra (one patient). The study disclosed normal findings in asymptomatic siblings. MRS showed decreased N-acetyl-aspartate/creatine ratio at the basal ganglia in encephalopathic patients when compared to a group of sex- and age-matched controls. CONCLUSIONS: Brain injury in GA-I is characterized by the presence of cytotoxic edema and reduced neuronal integrity by functional imaging techniques. Involvement of the basal ganglia may be asymmetrical in patients with unilateral motor disorder and may extent to the cerebral peduncles and substantia nigra, which may be responsible for the acute onset dystonia in some patients. Functional techniques failed to demonstrate any abnormalities in asymptomatic patients, which is in agreement with the integrity of basal ganglia structures observed by conventional MRI sequences.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/complicações , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Lesões Encefálicas/diagnóstico , Lesões Encefálicas/etiologia , Glutaril-CoA Desidrogenase/deficiência , Erros Inatos do Metabolismo dos Aminoácidos/urina , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Encéfalo/patologia , Lesões Encefálicas/urina , Mapeamento Encefálico , Creatina/metabolismo , Glutaratos/metabolismo , Glutaratos/urina , Glutaril-CoA Desidrogenase/genética , Humanos , Lactente , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Estudos RetrospectivosRESUMO
A computer-based decision support system to assist radiologists in diagnosing and grading brain tumours has been developed by the multi-centre INTERPRET project. Spectra from a database of 1H single-voxel spectra of different types of brain tumours, acquired in vivo from 334 patients at four different centres, are clustered according to their pathology, using automated pattern recognition techniques and the results are presented as a two-dimensional scatterplot using an intuitive graphical user interface (GUI). Formal quality control procedures were performed to standardize the performance of the instruments and check each spectrum, and teams of expert neuroradiologists, neurosurgeons, neurologists and neuropathologists clinically validated each case. The prototype decision support system (DSS) successfully classified 89% of the cases in an independent test set of 91 cases of the most frequent tumour types (meningiomas, low-grade gliomas and high-grade malignant tumours--glioblastomas and metastases). It also helps to resolve diagnostic difficulty in borderline cases. When the prototype was tested by radiologists and other clinicians it was favourably received. Results of the preliminary clinical analysis of the added value of using the DSS for brain tumour diagnosis with MRS showed a small but significant improvement over MRI used alone. In the comparison of individual pathologies, PNETs were significantly better diagnosed with the DSS than with MRI alone.
Assuntos
Neoplasias Encefálicas/diagnóstico , Bases de Dados Factuais , Sistemas de Apoio a Decisões Clínicas/organização & administração , Diagnóstico por Computador/métodos , Sistemas Inteligentes , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Algoritmos , Humanos , Reconhecimento Automatizado de Padrão/métodos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: We sought to evaluate whether taurine detection in short-echo (20 ms) proton magnetic resonance spectroscopy contributes to the noninvasive differential diagnosis between medulloblastoma and cerebellar astrocytoma in children and young adults. These two types of tumor have very different prognoses and may be difficult to differentiate by neuroradiological or clinical means. METHODS: Single-voxel proton magnetic resonance spectra of tumors were acquired at 1.5 T in 14 patients with biopsy-proven primary cerebellar tumors (six medulloblastomas, seven astrocytomas, and one mixed astroependymoma) using short-echo time (20 ms) and long-echo time (135 ms). For taurine assignment, qualitative analysis was performed on short-echo time spectra and results were compared in vitro with spectra of model solutions. Perchloric acid extracts of postsurgical tumor biopsies were performed in two medulloblastoma cases. RESULTS: Taurine detection was demonstrated in all patients with medulloblastoma and in none of those with astrocytoma. We were unable to ascertain any relationship between taurine and metastatic spread within the medulloblastoma group. CONCLUSION: Medulloblastomas characteristically seem to show taurine detectable in vivo by short-echo proton magnetic resonance spectroscopy, which may help to discriminate medulloblastoma from cerebellar astrocytoma.