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With the arrival of disease-modifying drugs, neurodegenerative diseases will require an accurate diagnosis for optimal treatment. Convolutional neural networks are powerful deep learning techniques that can provide great help to physicians in image analysis. The purpose of this study is to introduce and validate a 3D neural network for classification of Alzheimer's disease (AD), frontotemporal dementia (FTD) or cognitively normal (CN) subjects based on brain glucose metabolism. Retrospective [18F]-FDG-PET scans of 199 CE, 192 FTD and 200 CN subjects were collected from our local database, Alzheimer's disease and frontotemporal lobar degeneration neuroimaging initiatives. Training and test sets were created using randomization on a 90 %-10 % basis, and training of a 3D VGG16-like neural network was performed using data augmentation and cross-validation. Performance was compared to clinical interpretation by three specialists in the independent test set. Regions determining classification were identified in an occlusion experiment and Gradient-weighted Class Activation Mapping. Test set subjects were age- and sex-matched across categories. The model achieved an overall 89.8 % accuracy in predicting the class of test scans. Areas under the ROC curves were 93.3 % for AD, 95.3 % for FTD, and 99.9 % for CN. The physicians' consensus showed a 69.5 % accuracy, and there was substantial agreement between them (kappa = 0.61, 95 % CI: 0.49-0.73). To our knowledge, this is the first study to introduce a deep learning model able to discriminate AD and FTD based on [18F]-FDG PET scans, and to isolate CN subjects with excellent accuracy. These initial results are promising and hint at the potential for generalization to data from other centers.
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Doença de Alzheimer , Demência Frontotemporal , Humanos , Doença de Alzheimer/diagnóstico por imagem , Fluordesoxiglucose F18 , Demência Frontotemporal/diagnóstico por imagem , Estudos Retrospectivos , Encéfalo/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Redes Neurais de ComputaçãoRESUMO
Epilepsy is one of the most frequent neurological conditions with an estimated prevalence of more than 50 million people worldwide and an annual incidence of two million. Although pharmacotherapy with anti-seizure medication (ASM) is the treatment of choice, ~30% of patients with epilepsy do not respond to ASM and become drug resistant. Focal epilepsy is the most frequent form of epilepsy. In patients with drug-resistant focal epilepsy, epilepsy surgery is a treatment option depending on the localisation of the seizure focus for seizure relief or seizure freedom with consecutive improvement in quality of life. Beside examinations such as scalp video/electroencephalography (EEG) telemetry, structural, and functional magnetic resonance imaging (MRI), which are primary standard tools for the diagnostic work-up and therapy management of epilepsy patients, molecular neuroimaging using different radiopharmaceuticals with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) influences and impacts on therapy decisions. To date, there are no literature-based praxis recommendations for the use of Nuclear Medicine (NM) imaging procedures in epilepsy. The aims of these guidelines are to assist in understanding the role and challenges of radiotracer imaging for epilepsy; to provide practical information for performing different molecular imaging procedures for epilepsy; and to provide an algorithm for selecting the most appropriate imaging procedures in specific clinical situations based on current literature. These guidelines are written and authorized by the European Association of Nuclear Medicine (EANM) to promote optimal epilepsy imaging, especially in the presurgical setting in children, adolescents, and adults with focal epilepsy. They will assist NM healthcare professionals and also specialists such as Neurologists, Neurophysiologists, Neurosurgeons, Psychiatrists, Psychologists, and others involved in epilepsy management in the detection and interpretation of epileptic seizure onset zone (SOZ) for further treatment decision. The information provided should be applied according to local laws and regulations as well as the availability of various radiopharmaceuticals and imaging modalities.
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Epilepsia , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada de Emissão de Fóton Único , Humanos , Epilepsia/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Tomografia por Emissão de Pósitrons/normas , Medicina Nuclear , Europa (Continente)RESUMO
The present procedural guidelines summarize the current views of the EANM Neuro-Imaging Committee (NIC). The purpose of these guidelines is to assist nuclear medicine practitioners in making recommendations, performing, interpreting, and reporting results of [18F]FDG-PET imaging of the brain. The aim is to help achieve a high-quality standard of [18F]FDG brain imaging and to further increase the diagnostic impact of this technique in neurological, neurosurgical, and psychiatric practice. The present document replaces a former version of the guidelines that have been published in 2009. These new guidelines include an update in the light of advances in PET technology such as the introduction of digital PET and hybrid PET/MR systems, advances in individual PET semiquantitative analysis, and current broadening clinical indications (e.g., for encephalitis and brain lymphoma). Further insight has also become available about hyperglycemia effects in patients who undergo brain [18F]FDG-PET. Accordingly, the patient preparation procedure has been updated. Finally, most typical brain patterns of metabolic changes are summarized for neurodegenerative diseases. The present guidelines are specifically intended to present information related to the European practice. The information provided should be taken in the context of local conditions and regulations.
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Fluordesoxiglucose F18 , Medicina Nuclear , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Fluordesoxiglucose F18/metabolismo , Humanos , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: To examine and compare longitudinal changes of cortical glucose metabolism in amnestic and non-amnestic sporadic forms of early-onset Alzheimer's disease and assess potential associations with neuropsychological performance over a 3-year period time. METHODS: Eighty-two participants meeting criteria for early-onset (< 65 years) sporadic form of probable Alzheimer's disease and presenting with a variety of clinical phenotypes (47 amnestic and 35 non-amnestic forms) were included at baseline and followed up for 1.44 ± 1.23 years. All of the participants underwent a work-up at baseline and every year during the follow-up period, which includes clinical examination, neuropsychological testing, genotyping, cerebrospinal fluid biomarker assays, and structural MRI and 18F-FDG PET. Vertex-wise partial volume-corrected glucose metabolic maps across the entire cortical surface were generated and longitudinally assessed together with the neuropsychological scores using linear mixed-effects modeling as a function of amnestic and non-amnestic sporadic forms of early-onset Alzheimer's disease. RESULTS: Similar evolution patterns of glucose metabolic decline between amnestic and non-amnestic forms were observed in widespread neocortical cortices. However, only non-amnestic forms appeared to have a greater reduction of glucose metabolism in lateral orbitofrontal and bilateral medial temporal cortices associated with more severe declines of neuropsychological performance compared with amnestic forms. Furthermore, results suggest that glucose metabolic decline in amnestic forms would progress along an anterior-to-posterior axis, whereas glucose metabolic decline in non-amnestic forms would progress along a posterior-to-anterior axis. CONCLUSIONS: We found differences in spatial distribution and temporal trajectory of glucose metabolic decline between amnestic and non-amnestic early-onset Alzheimer's disease groups, suggesting that one might want to consider treating the two forms of the disease as two separate entities.
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Doença de Alzheimer , Fluordesoxiglucose F18 , Doença de Alzheimer/diagnóstico por imagem , Encéfalo , Humanos , Imageamento por Ressonância Magnética , Testes Neuropsicológicos , Tomografia por Emissão de PósitronsRESUMO
PURPOSE: This joint practice guideline or procedure standard was developed collaboratively by the European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI). The goal of this guideline is to assist nuclear medicine practitioners in recommending, performing, interpreting, and reporting the results of dopaminergic imaging in parkinsonian syndromes. METHODS: Currently nuclear medicine investigations can assess both presynaptic and postsynaptic function of dopaminergic synapses. To date both EANM and SNMMI have published procedural guidelines for dopamine transporter imaging with single photon emission computed tomography (SPECT) (in 2009 and 2011, respectively). An EANM guideline for D2 SPECT imaging is also available (2009). Since the publication of these previous guidelines, new lines of evidence have been made available on semiquantification, harmonization, comparison with normal datasets, and longitudinal analyses of dopamine transporter imaging with SPECT. Similarly, details on acquisition protocols and simplified quantification methods are now available for dopamine transporter imaging with PET, including recently developed fluorinated tracers. Finally, [18F]fluorodopa PET is now used in some centers for the differential diagnosis of parkinsonism, although procedural guidelines aiming to define standard procedures for [18F]fluorodopa imaging in this setting are still lacking. CONCLUSION: All these emerging issues are addressed in the present procedural guidelines for dopaminergic imaging in parkinsonian syndromes.
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Medicina Nuclear , Transtornos Parkinsonianos , Humanos , Imagem Molecular , Transtornos Parkinsonianos/diagnóstico por imagem , Cintilografia , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
PURPOSE: The purpose of the study was to determine the correlations between brain metabolism and cognitive impairment in patients with drug-resistant mesial temporal lobe epilepsy (MTLE). METHODS: [18F]-FluoroDeoxyGlucose positron emission tomography ([18F]-FDG-PET) and neuropsychological assessment were performed in 97 patients with MTLE (53 females, 15-56â¯years old, mean: 31.6â¯years, standard deviation (SD)â¯=â¯10.4) with unilateral hippocampal sclerosis (HS, 49 left). We compared brain metabolism and gray matter volume (GMV) between patients with cognitive impairment (intelligence quotient (IQ) and memory index <80) and patients with normal cognition, using statistical parametric mapping (SPM), in the whole population then in right and left HS (RHS, LHS) separately. RESULTS: Intelligence quotient (40-121, mean: 83.7⯱â¯16.9) and memory index (45-133, mean: 80.7⯱â¯19.3) were impaired in 43% and 51% of the patients, respectively, similarly in RHS and LHS. We did not find any correlations between IQ and clinical factors related to epilepsy; however, there was a significant correlation between low memory index and early age of onset in LHS (pâ¯=â¯0.021), and widespread epileptogenic zone in the whole population (pâ¯=â¯0.033). Impaired IQ correlated with extratemporal hypometabolism, involving frontoparietal networks implicated in the default mode network (DMN), predominantly in the midline cortices. Metabolic asymmetry regarding HS lateralization included the precuneus (pC) in LHS and the anterior cingulate cortex (ACC) in RHS, both areas corresponding to key nodes of the DMN. Memory index correlated with the same frontoparietal networks as for IQ, with an additional involvement of the temporal lobes, which was ipsilateral in RHS and contralateral in LHS. A diffuse decrease of GMV including the ipsilateral hippocampus correlated with cognitive impairment; however, the structural alterations did not match with the hypometabolic areas. CONCLUSIONS: Cognitive impairment in MTLE correlates with extratemporal hypometabolism, involving the mesial frontoparietal networks implicated in the DMN and suggesting a disconnection with the affected hippocampus. Asymmetric alterations of connectivity may sustain the predominant ACC and pC metabolic decrease in patients with cognitive impairment.
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Córtex Cerebral/metabolismo , Disfunção Cognitiva/metabolismo , Epilepsia do Lobo Temporal/metabolismo , Rede Nervosa/metabolismo , Lobo Parietal/metabolismo , Lobo Temporal/metabolismo , Adolescente , Adulto , Córtex Cerebral/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/epidemiologia , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/epidemiologia , Feminino , Fluordesoxiglucose F18/metabolismo , Hipocampo/diagnóstico por imagem , Hipocampo/metabolismo , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Memória/fisiologia , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Testes Neuropsicológicos , Lobo Parietal/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Lobo Temporal/diagnóstico por imagem , Adulto JovemRESUMO
PURPOSE: One can reasonably suppose that cerebrospinal spinal fluid (CSF) biomarkers can identify distinct subgroups of Alzheimer's disease (AD) patients. In order to better understand differences in CSF biomarker patterns, we used FDG PET to assess cerebral metabolism in CSF-based subgroups of AD patients. METHODS: Eighty-five patients fulfilling the criteria for probable early-onset AD (EOAD) underwent lumbar puncture, brain 18F-FDG PET and MRI. A cluster analysis was performed, with the CSF biomarkers for AD as variables. Vertex-wise, partial-volume-corrected metabolic maps were computed for the patients and compared between the clusters of patients. Linear correlations between each CSF biomarker and the metabolic maps were assessed. RESULTS: Three clusters emerged. The "Aß42" cluster contained 32 patients with low levels of Aß42, while tau and p-tau remained within the normal range. The "Aß42 + tau" cluster contained 41 patients with low levels of Aß42 and high levels of tau and p-tau. Lastly, the "tau" cluster contained 12 patients with very high levels of tau and p-tau and low-normal levels of Aß42. There were no inter-cluster differences in age, sex ratio, educational level, APOE genotype, disease duration or disease severity. The "Aß42 + tau" and "tau" clusters displayed more marked frontal hypometabolism than the "Aß42" cluster did, and frontal metabolism was significantly negatively correlated with the CSF tau level. The "Aß42" and "Aß42 + tau" clusters displayed more marked hypometabolism in the left occipitotemporal region than the "tau" cluster did, and metabolism in this region was significantly and positively correlated with the CSF Aß42 level. CONCLUSION: The CSF biomarkers can be used to identify metabolically distinct subgroups of patients with EOAD. Future research should seek to establish whether these biochemical differences have clinical consequences.
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Doença de Alzheimer/líquido cefalorraquidiano , Encéfalo/metabolismo , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Encéfalo/diagnóstico por imagem , Análise por Conglomerados , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/líquido cefalorraquidiano , Fosfoproteínas/líquido cefalorraquidiano , Tomografia por Emissão de Pósitrons , Proteínas tau/líquido cefalorraquidiano , Proteínas tau/metabolismoRESUMO
The original version of this article has added numbers in the text which are unnecessary. Correct line should be: "We also performed PET/MRI based surgical resections in an increasing number of MRI negative/ doubtful cases with favourable outcome."
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PURPOSE: To assess the localizing value of 18F-FDG PET in patients operated on for drug-resistant epilepsy due to focal cortical dysplasia type 2 (FCD2). METHODS: We analysed 18F-FDG PET scans from 103 consecutive patients (52 males, 7-65 years old) with histologically proven FCD2. PET and MRI data were first reviewed by visual analysis blinded to clinical information and FCD2 location. The additional value of electroclinical data and PET/MRI coregistration was assessed by comparison with pathological results and surgical outcomes. RESULTS: Visual analysis of PET scans showed focal or regional hypometabolism corresponding to the FCD2 in 45 patients (44%), but the findings were doubtful or misleading in 37 patients and negative in 21. When considering electroclinical data, positive localization was obtained in 73 patients, and this increased to 85 (83%) after coregistration of PET and MRI data. Under the same conditions, MRI was positive in 61 patients (59%), doubtful in 15 and negative in 27. The additional value of PET was predominant in patients negative or doubtful on MRI, localizing the FCD2 in 35 patients (83%). Interobserver agreement correlated with the grade of hypometabolism: it was good in patients with mild to severe hypometabolism (82-95%), but moderate in those with subtle/doubtful hypometabolism (45%). The main factors influencing positive PET localization were the grade of hypometabolism and the size of the FCD2 (P < 0.0001). Misleading location (nine patients) was associated with a small FCD2 in the mesial frontal and central regions. Following limited cortical resection mainly located in extratemporal areas (mean follow-up 5.6 years), a seizure-free outcome was achieved in 94% of patients, including Engel's class IA in 72%. CONCLUSION: In this series, 18F-FDG PET contributed to the localization of FCD2 in 83% of patients. This high localizing value was obtained by integration of electroclinical data and PET/MRI coregistration. This approach may help improve the surgical outcome in extratemporal epilepsy, even in patients negative on MRI.
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Eletroencefalografia , Epilepsia/diagnóstico por imagem , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Adolescente , Adulto , Idoso , Criança , Feminino , Fluordesoxiglucose F18 , França , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
INTRODUCTION: Although some studies have previously addressed the clinical impact of amyloid positron emission tomography (PET), none has specifically addressed its selective and hierarchical implementation in relation to cerebrospinal fluid analysis in a naturalistic setting. METHODS: This multicenter study was performed at French tertiary memory clinics in patients presenting with most complex clinical situations (i.e., early-onset, atypical clinical profiles, suspected mixed etiological conditions, unexpected rate of progression), for whom cerebrospinal fluid analysis was indicated but either not feasible or considered as noncontributory (ClinicalTrials.gov: NCT02681172). RESULTS: Two hundred five patients were enrolled with evaluable florbetaben PET scans; 64.4% of scans were amyloid positive. PET results led to changed diagnosis and improved confidence in 66.8% and 81.5% of patients, respectively, and altered management in 80.0% of cases. DISCUSSION: High-level improvement of diagnostic certainty and management is provided by selective and hierarchical implementation of florbetaben PET into current standard practices for the most complex dementia cases.
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Amiloide/metabolismo , Compostos de Anilina , Encéfalo/diagnóstico por imagem , Demência/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Estilbenos , Idoso , Encéfalo/metabolismo , Demência/metabolismo , Diagnóstico Diferencial , Feminino , França , Humanos , MasculinoRESUMO
OBJECTIVE: To determine the main factors influencing metabolic changes in mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis (HS). METHODS: We prospectively studied 114 patients with MTLE (62 female; 60 left HS; 15- to 56-year-olds) with (18) F-fluorodeoxyglucose-positron emission tomography and correlated the results with the side of HS, structural atrophy, electroclinical features, gender, age at onset, epilepsy duration, and seizure frequency. Imaging processing was performed using statistical parametric mapping. RESULTS: Ipsilateral hypometabolism involved temporal (mesial structures, pole, and lateral cortex) and extratemporal areas including the insula, frontal lobe, perisylvian regions, and thalamus, more extensively in right HS (RHS). A relative increase of metabolism (hypermetabolism) was found in the nonepileptic temporal lobe and in posterior areas bilaterally. Voxel-based morphometry detected unilateral hippocampus atrophy and gray matter concentration decrease in both frontal lobes, more extensively in left HS (LHS). Regardless of the structural alterations, the topography of hypometabolism correlated strongly with the extent of epileptic networks (mesial, anterior-mesiolateral, widespread mesiolateral, and bitemporal according to the ictal spread), which were larger in RHS. Notably, widespread perisylvian and bitemporal hypometabolism was found only in RHS. Mirror hypermetabolism was grossly proportional to the hypometabolic areas, coinciding partly with the default mode network. Gender-related effect was significant mainly in the contralateral frontal lobe, in which metabolism was higher in female patients. Epilepsy duration correlated with the contralateral temporal metabolism, positively in LHS and negatively in RHS. Opposite results were found with age at onset. High seizure frequency correlated negatively with the contralateral metabolism in LHS. SIGNIFICANCE: Epileptic networks, as assessed by electroclinical correlations, appear to be the main determinant of hypometabolism in MTLE. Compensatory mechanisms reflected by a relative hypermetabolism in the nonepileptic temporal lobe and in extratemporal areas seem more efficient in LHS and in female patients, whereas long duration, late onset of epilepsy, and high seizure frequency may reduce these adaptive changes.
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Encéfalo/metabolismo , Epilepsia do Lobo Temporal/patologia , Adolescente , Adulto , Idade de Início , Análise de Variância , Anticonvulsivantes/uso terapêutico , Encéfalo/diagnóstico por imagem , Estudos de Coortes , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/tratamento farmacológico , Feminino , Fluordesoxiglucose F18 , Lateralidade Funcional , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Fatores Sexuais , Adulto JovemRESUMO
OBJECTIVE: Despite its well-known effectiveness, the cost-effectiveness of epilepsy surgery has never been demonstrated in France. We compared cost-effectiveness between resective surgery and medical therapy in a controlled cohort of adult patients with partial intractable epilepsy. METHODS: A prospective cohort of adult patients with surgically remediable and medically intractable partial epilepsy was followed over 5 years in the 15 French centers. Effectiveness was defined as 1 year without a seizure, based on the International League Against Epilepsy (ILAE) classification. Clinical outcomes and direct costs were compared between surgical and medical groups. Long-term direct costs and effectiveness were extrapolated over the patients' lifetimes with a Monte-Carlo simulation using a Markov model, and an incremental cost-effectiveness ratio (ICER) was computed. Indirect costs were also evaluated. RESULTS: Among the 289 enrolled surgery candidates, 207 were operable-119 in the surgical group and 88 in the medical group-65 were not operable and not analyzed here, 7 were finally not eligible, and 10 were not followed. The proportion of patients completely seizure-free during the last 12 months (ILAE class 1) was 69.0% in the operated group and 12.3% in the medical group during the second year (p < 0.001), and it was respectively 76.8% and 21% during the fifth year (p < 0.001). Direct costs became significantly lower in the surgical group the third year after surgery, as a result of less antiepileptic drug use. The value of the discounted ICER was 10,406 (95% confidence interval [CI] 10,182-10,634) at 2 years and 2,630 (CI 95% 2,549-2,713) at 5 years. Surgery became cost-effective between 9 and 10 years after surgery, and even earlier if indirect costs were taken into account as well. SIGNIFICANCE: Our study suggests that in addition to being safe and effective, resective surgery of epilepsy is cost-effective in the medium term. It should therefore be considered earlier in the development of epilepsy.
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Epilepsias Parciais/economia , Epilepsias Parciais/cirurgia , Procedimentos Neurocirúrgicos/economia , Procedimentos Neurocirúrgicos/métodos , Adolescente , Adulto , Anticonvulsivantes/economia , Anticonvulsivantes/uso terapêutico , Estudos de Coortes , Análise Custo-Benefício , Atenção à Saúde/economia , Atenção à Saúde/métodos , Epilepsia Resistente a Medicamentos , Epilepsias Parciais/tratamento farmacológico , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do Tratamento , Adulto JovemAssuntos
Betacoronavirus , Infecções por Coronavirus , Neuroimagem/métodos , Serviço Hospitalar de Medicina Nuclear/organização & administração , Pandemias , Pneumonia Viral , Encéfalo/diagnóstico por imagem , Encéfalo/virologia , COVID-19 , Ensaios Clínicos como Assunto , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/epidemiologia , Atenção à Saúde , Demência/terapia , Acessibilidade aos Serviços de Saúde , Necessidades e Demandas de Serviços de Saúde , Humanos , Doenças do Sistema Nervoso/complicações , Doenças do Sistema Nervoso/diagnóstico por imagem , Doenças do Sistema Nervoso/virologia , Neuroimagem/estatística & dados numéricos , Estudos Observacionais como Assunto , Transtornos do Olfato/etiologia , Transtornos do Olfato/virologia , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/epidemiologia , Tomografia por Emissão de Pósitrons , Quarentena , SARS-CoV-2 , Trombofilia/etiologia , Trombofilia/virologia , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
AIM: The aim of this study was to evaluate the impact of two different therapeutic strategies in patients with partial seizures who were intractable to the first prescribed antiepileptic drug (AED); alternative monotherapy vs early add-on treatment. METHODS: We conducted an open, cluster-randomised, prospective, controlled trial in patients with persistent partial seizures, despite treatment with one AED, who were never administered any other AEDs. Neurologists were randomised to two strategies: in group A, an alternative monotherapy with a second AED was employed; in group B, add-on treatment with a second AED was employed. The primary outcome was the percentage of seizure-free patients during a two-month period after six months of treatment. The secondary outcomes were: (i) the percentage of patients achieving a 50% reduction in the number of seizures at six months; (ii) the quality of life based on the Quality Of Life In Epilepsy scale; and (iii) tolerability. RESULTS: A total of 143 neurologists were included and randomised, and 264 patients were evaluated. At six months, the primary outcome was 51% in group A and 45% in group B (p=0.34). The percentage of patients achieving a 50% reduction in the number of seizures at six months was 76% in group A and 84% in group B (p=0.53). The quality of life and the tolerability did not significantly differ between the two groups. CONCLUSIONS: Alternative monotherapy or early treatment initiation with another AED drug resulted in similar efficacy, and the side effects associated with monotherapy and combined therapies were similar, which suggests that individual susceptibility is more important than the number and burden of AEDs used.
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Anticonvulsivantes/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Adolescente , Adulto , Idoso , Anticonvulsivantes/efeitos adversos , Quimioterapia Combinada , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento , Adulto JovemRESUMO
Theory of mind reasoning-the ability to understand someone else's mental states, such as beliefs, intentions and desires-is crucial in social interaction. It has been suggested that a theory of mind deficit may account for some of the abnormalities in interpersonal behaviour that characterize patients affected by behavioural variant frontotemporal dementia. However, there are conflicting reports as to whether understanding someone else's mind is a key difference between behavioural variant frontotemporal dementia and other neurodegenerative conditions such as Alzheimer's disease. Literature data on the relationship between theory of mind abilities and executive functions are also contradictory. These disparities may be due to underestimation of the fractionation within theory of mind components. A recent theoretical framework suggests that taking someone else's mental perspective requires two distinct processes: inferring someone else's belief and inhibiting one's own belief, with involvement of the temporoparietal and right frontal cortices, respectively. Therefore, we performed a neuropsychological and neuroimaging study to investigate the hypothesis whereby distinct cognitive deficits could impair theory of mind reasoning in patients with Alzheimer's disease and patients with behavioural variant frontotemporal dementia. We used a three-option false belief task to assess theory of mind components in 11 patients with behavioural variant frontotemporal dementia, 12 patients with Alzheimer's disease and 20 healthy elderly control subjects. The patients with behavioural variant frontotemporal dementia and those with Alzheimer's disease were matched for age, gender, education and global cognitive impairment. [(18)F]-fluorodeoxyglucose-positron emission tomography imaging was used to investigate neural correlates of theory of mind reasoning deficits. Performance in the three-option false belief task revealed differential impairments in the components of theory of mind reasoning; patients with Alzheimer's disease had a predominant deficit in inferring someone else's belief, whereas patients with behavioural variant frontotemporal dementia were selectively impaired in inhibiting their own mental perspective. Moreover, inhibiting one's own perspective was strongly correlated with inhibition in a Stroop task but not with other subprocesses of executive functions. This finding suggests that self-perspective inhibition may depend on cognitive processes that are not specific to the social domain. Last, the severity of the deficit in inferring someone else's beliefs correlated significantly over all subjects with hypometabolism in the left temporoparietal junction, whereas the severity of the deficit in self-perspective inhibition correlated significantly with hypometabolism in the right lateral prefrontal cortex. In conclusion, our findings provided clinical and imaging evidence to support differential deficits in two components of theory of mind reasoning (subserved by distinct brain regions) in patients with Alzheimer's disease and patients with behavioural variant frontotemporal dementia.
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Doença de Alzheimer/fisiopatologia , Demência Frontotemporal/fisiopatologia , Teoria da Mente/fisiologia , Idoso , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Testes NeuropsicológicosRESUMO
Prostate cancer is one of the most common forms of cancer in men. An imaging technique for its diagnosis is [68Ga]-prostate-specific membrane antigen ([68Ga]Ga-PSMA-11) positron emission tomography (PET). To address the increasing demand for [68Ga]-labeled peptides and reduce the cost of radiosynthesis, it is therefore necessary to optimize the elution process of [68Ge]Ge/[68Ga]Ga generators. This study aims to identify the most effective approach for optimizing radiosynthesis using double elution in parallel of two [68Ge]Ge/[68Ga]Ga generators. Two methods have been tested: one using prepurification, and the other using fractionated elution. Five synthesis sequences were conducted using each method. The mean labeling yields for double elution with prepurification were 45.8 ± 29.4 (mean ± standard deviation) and none met the required criteria. The mean labeling yields for the fractionated double elution were 97.5 ± 1.9 (mean ± standard deviation) meeting the criteria, significantly superior to the prepurification method (p = 0.012), and similar to those of simple elution. This study showed that fractionated double elution from [68Ge]Ge/[68Ga]Ga generators produced a significantly higher labeling yield than double elution with prepurification, resulting in a larger activity recovered via radiosynthesis, thereby allowing more diagnostic tests to be performed.
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BACKGROUND: Cardiac uptake on technetium-99m whole-body scintigraphy (WBS) is almost pathognomonic of transthyretin cardiac amyloidosis. The rare false positives are often related to light-chain cardiac amyloidosis. However, this scintigraphic feature remains largely unknown, leading to misdiagnosis despite characteristic images. A retrospective review of all WBSs in a hospital database to detect those with cardiac uptake may allow the identification of undiagnosed patients. OBJECTIVES: The authors sought to develop and validate a deep learning-based model that automatically detects significant cardiac uptake (Perugini grade ≥2) on WBS from large hospital databases in order to retrieve patients at risk of cardiac amyloidosis. METHODS: The model is based on a convolutional neural network with image-level labels. The performance evaluation was performed with C-statistics using a 5-fold cross-validation scheme stratified so that the proportion of positive and negative WBSs remained constant across folds and using an external validation data set. RESULTS: The training data set consisted of 3,048 images: 281 positives (Perugini grade ≥2) and 2,767 negatives. The external validation data set consisted of 1,633 images: 102 positives and 1,531 negatives. The performance of the 5-fold cross-validation and external validation was as follows: 98.9% (± 1.0) and 96.1% for sensitivity, 99.5% (± 0.4) and 99.5% for specificity, and 0.999 (SD = 0.000) and 0.999 for the area under the curve of the receiver-operating characteristic curves. Sex, age <90 years, body mass index, injection-acquisition delay, radionuclides, and the indication of WBS only slightly affected performances. CONCLUSIONS: The authors' detection model is effective at identifying patients with cardiac uptake Perugini grade ≥2 on WBS and may help in the diagnosis of patients with cardiac amyloidosis.