Genetics, clinical features and outcomes of non-syndromic pituitary gigantism: experience of a single center from Sao Paulo, Brazil.

PURPOSE: Non-syndromic pituitary gigantism (PG) is a very rare disease. Aryl hydrocarbon receptor-interacting protein (AIP) and G protein-coupled receptor 101 (GPR101) genetic abnormalities represent important etiologic causes of PG and may account for up to 40% of these cases. Here, we aimed to characterize the clinical and molecular findings and long-term outcomes in 18 patients (15 males, three females) with PG followed at a single tertiary center in Sao Paulo, Brazil. METHODS: Genetic testing for AIP and GPR101 were performed by DNA sequencing, droplet digital PCR and array comparative genomic hybridization (aCGH). RESULTS: Pathogenic variants in the AIP gene were detected in 25% of patients, including a novel variant in splicing regulatory sequences which was present in a sporadic male case. X-LAG due to GPR101 microduplication was diagnosed in two female patients (12.5%). Of interest, these patients had symptoms onset by age 5 and 9 years old and diagnosis at 5 and 15 years, respectively. X-LAG, but not AIP, patients had a significantly lower age of symptoms onset and diagnosis and a higher height Z-score when compared to non-X-LAG. No other differences in clinical features and/or treatment outcomes were observed among PG based on their genetic background. CONCLUSION: We characterize the clinical and molecular findings and long-term outcome of the largest single-center PG cohort described so far.

Substantia nigra fractional anisotropy is not a diagnostic biomarker of Parkinson's disease: A diagnostic performance study and meta-analysis.

OBJECTIVES: Our goal was to estimate the diagnostic accuracy of substantia nigra fractional anisotropy (SN-FA) for Parkinson's disease (PD) diagnosis in a sample similar to the clinical setting, including patients with essential tremor (ET) and healthy controls (HC). We also performed a systematic review and meta-analysis to estimate mean change in SN-FA induced by PD and its diagnostic accuracy. METHODS: Our sample consisted of 135 subjects: 72 PD, 21 ET and 42 HC. To address inter-scanner variability, two 3.0-T MRI scans were performed. MRI results of this sample were pooled into a meta-analysis that included 1,432 subjects (806 PD and 626 HC). A bivariate model was used to evaluate diagnostic accuracy measures. RESULTS: In our sample, we did not observe a significant effect of disease on SN-FA and it was uninformative for diagnosis. The results of the meta-analysis estimated a 0.03 decrease in mean SN-FA in PD relative to HC (CI: 0.01-0.05). However, the discriminatory capability of SN-FA to diagnose PD was low: pooled sensitivity and specificity were 72 % (CI: 68-75) and 63 % (CI: 58-70), respectively. There was high heterogeneity between studies (I2 = 91.9 %). CONCLUSIONS: SN-FA cannot be used as an isolated measure to diagnose PD. KEY POINTS: • SN-FA appears insufficiently sensitive and specific to diagnose PD. • Radiologists must be careful when translating mean group results to clinical practice. • Imaging protocol and analysis standardization is necessary for developing reproducible quantitative biomarkers.

Detection of the source of hemorrhage using postmortem computerized tomographic angiography in a case of a giant juvenile nasopharyngeal angiofibroma after surgical treatment.

PURPOSE: Postmortem computerized tomographic angiography (PMCTA) has been increasingly used in forensic medicine to detect and locate the source of bleeding in cases of fatal acute hemorrhage. In this paper, we report a case of postoperative complication in a patient with a giant juvenile nasopharyngeal angiofibroma in which the source of bleeding was detected by PMCTA. METHODS: A case description and evaluations of the pre- and postoperative exams, postmortem CT angiogram, and conventional autopsy results are provided. RESULTS: The source of bleeding was identified by postmortem CT angiography but not by conventional autopsy. The established protocol, injecting contrast medium into the femoral artery, was effective in identifying the source of bleeding. CONCLUSIONS: Postoperative bleeding is a rare and frequently fatal complication of juvenile nasopharyngeal angiofibroma. As a complement to conventional autopsy, postmortem angiography is a valuable tool for the detection of lethal acute hemorrhagic foci, and establishing a routine procedure for PMCTA may improve its efficiency.

Survivin: A Potential Marker of Resistance to Somatostatin Receptor Ligands.

CONTEXT: Invasive and somatostatin receptor ligand (SRL)-resistant pituitary tumors represent a challenge in the clinical practice of endocrinologists. Efforts have been made to elucidate reliable makers for both. Survivin and eukaryotic translation initiation factor-binding protein 1 (4EBP1) are upregulated in several cancers and involved in apoptosis and cell proliferation. OBJECTIVE: We explored the role of these markers in somatotropinomas. METHODS: Immunostains for survivin and 4EBP1, and also for somatostatin receptor type 2 (SSTR2), Ki-67, and cytokeratin 18, were analyzed in tissue microarrays containing 52 somatotropinoma samples. Tumor invasiveness was evaluated in all samples while drug resistance was evaluated in 34 patients who received SRL treatment. All these parameters were correlated with first-generation SRL (fg-SRL) responsiveness and tumor invasiveness. RESULTS: Low survivin expression (P = 0.04), hyperintense signal on T2 weighted image (T2WI) (P = 0.01), younger age (P = 0.01), sparsely granular adenomas (SGA) (P = 0.04), high postoperative growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels (P = 0.049 and P < 0.001, respectively), and large postoperative tumor size (P = 0.02) were associated with resistance to fg-SRL. Low survivin and SSTR2 expression and high 4EBP1 expression were associated with SGA (P = 0.04, P = 0.01, and P = 0.001, respectively). Younger age (P = 0.03), large tumor pre- and postoperative (P = 0.04 and P = 0.006, respectively), low SSTR2 expression (P = 0.03), and high baseline GH and IGF-1 (P = 0.01 and P = 0.02, respectively) were associated with tumor invasiveness. However, survivin, 4EBP1, Ki-67, and granulation patterns were not associated with tumor invasion. CONCLUSION: This study suggests that low survivin expression is predictive of resistance to fg-SRL in somatotropinomas, but not of tumor invasiveness.

Magnetic resonance imaging of the cranial nerves in infectious, neoplastic, and demyelinating diseases, as well as other inflammatory diseases: a pictorial essay.

The cranial nerves, which represent extensions of the functional structures of the brain, traverse the head and neck. They are connected to various cranial structures and are associated with several diseases. An in-depth understanding of their complex anatomy and normal imaging appearance allows the examiner to identify and characterize abnormalities with greater precision. One important tool for evaluating the cranial nerves is contrast-enhanced magnetic resonance imaging, especially that employing three-dimensional steady-state free precession sequences, which provide high soft-tissue and spatial resolution, despite the slen-derness of the nerves. In most cases of cranial nerve abnormalities, the imaging findings are nonspecific. Therefore, to narrow the differential diagnosis, it is necessary to take a full patient history, perform a focused physical examination, and order laboratory tests. In this pictorial essay, we review, illustrate, and discuss, from a pathophysiological perspective, infectious, neoplastic, and demyelinating disorders, as well as other inflammatory disorders, affecting the cranial nerves, the aim being to provide a practical, tangible reference for radiologists to use in daily practice.

Os nervos cranianos, que representam extensões das estruturas funcionais do cérebro, atravessam a cabeça e o pescoço. Eles estão conectados a várias estruturas cranianas e estão associados a várias doenças. Uma compreensão profunda de sua complexa anatomia e aparência normal por imagem permite ao examinador identificar e caracterizar as anormalidades com maior precisão. Uma ferramenta importante para avaliar os nervos cranianos é a ressonância magnética com contraste, especialmente as sequências tridimensionais steady-state free precession, que proporcionam alta resolução espacial e de partes moles, apesar da fina espessura dos nervos. Na maioria dos casos, os achados radiológicos não são específicos. Para estreitar o diagnóstico diferencial é necessário fazer uma anamnese completa do paciente, realizar um exame físico dirigido e solicitar testes laboratoriais. Neste ensaio iconográfico revisamos, ilustramos e discutimos, sob uma perspectiva fisiopatológica, os distúrbios infecciosos, neoplásicos, inflamatórios e desmielinizantes, visando a ser uma referência prática e tangível para a prática diária dos radiologistas.

Forging Connections in Latin America to Advance AI in Radiology.

The 1° Encontro Latino-Americano de IA em Saúde (1st Latin American Meeting on AI in Health) was held during the 2022 Jornada Paulista de Radiologia, the annual radiology meeting in the state of São Paulo. The event was created to foster discussion among Latin American countries about the complexity, challenges, and opportunities in developing and using artificial intelligence (AI) in those countries. Technological improvements in AI have created high expectations in health care. AI is recognized increasingly as a game changer in clinical radiology. To counter the fear that AI would "take over" radiology, the program included activities to educate radiologists. The development of AI in Latin America is in its early days, and although there are some pioneer cases, many regions still lack world-class technological infrastructure and resources. Legislation, regulation, and public policies in data privacy and protection, digital health, and AI are recent advances in many countries. The meeting program was developed with a broad scope, with expertise from different countries, backgrounds, and specialties, with the objective of encompassing all levels of complexity (from basic concepts to advanced techniques), perspectives (clinical, technical, ethical, and business), and specialties (both informatics and data science experts and the usual radiology clinical groups). It was an opportunity to connect with peers from other countries and share lessons learned about AI in health care in different countries and contexts. Keywords: Informatics, Use of AI in Education, Impact of AI on Education, Social Implications © RSNA, 2022.

Magnetic resonance imaging of the cranial nerves in congenital, traumatic, and vascular diseases: a pictorial essay.

The cranial nerves, which represent extensions of the functional structures of the brain, traverse the head and neck. They are connected to various cranial structures and are associated with several diseases. An in-depth understanding of their complex anatomy and normal imaging appearance allows the examiner to identify and characterize abnormalities with greater precision. One important tool for evaluating the cranial nerves is contrast-enhanced magnetic resonance imaging, especially three-dimensional steady-state free precession sequences, which provide high soft-tissue and spatial resolution, despite the slenderness of the nerves. In most cases, imaging findings are nonspecific. Therefore, to narrow the differential diagnosis, it is necessary to take a full patient anamnesis, perform a focused physical examination and order laboratory tests. In this pictorial essay we review, illustrate and discuss, from a pathophysiological perspective, congenital, traumatic, and vascular diseases of the cranial nerves.

Os nervos cranianos representam extensões das estruturas funcionais do cérebro que cruzam a cabeça e o pescoço. Eles estão ligados a diferentes estruturas cranianas e se relacionam com diversas doenças. Uma compreensão profunda de sua complexa anatomia e aparência normal de imagem permite ao examinador identificar e caracterizar com mais precisão as anormalidades. A ressonância magnética com contraste é uma importante ferramenta para avaliar essas estruturas, especialmente as sequências tridimensionais de precessão livre de estado estacionário, que proporcionam alta resolução espacial e de partes moles, apesar da fina espessura dos nervos cranianos. Na maioria dos casos, os achados de imagem são inespecíficos, e uma anamnese completa, exame físico dirigido e testes laboratoriais são necessários para estreitar o diagnóstico diferencial. Este ensaio iconográfico ilustra e discute doenças congênitas, traumáticas e vasculares dos nervos cranianos, mostrando imagens em uma abordagem fisiopatológica.

Quantitative evaluation of brain volume among elderly individuals in São Paulo, Brazil: a population-based study.

OBJECTIVE: To perform a quantitative analysis of the brain volume of elderly individuals in a population-based sample. MATERIALS AND METHODS: This was a radiological assessment and voxel-based quantitative analysis, with surface alignment, of 525 magnetic resonance imaging scans of individuals between 60 and 103 years of age who participated in the Saúde, Bem-estar e Envelhecimento (Health, Well-being, and Aging) study in the city of São Paulo, Brazil. RESULTS: We noted a median rate of reduction in total brain volume of 2.4% per decade after 60 years of age. Gray and white matter both showed volume reductions with age. The total brain volume/intracranial brain volume ratio differed between males and females. CONCLUSION: We have corroborated the findings of studies conducted in the United States and Europe. The total brain volume/intracranial brain volume ratio is higher in men, representing a potential bias for the conventional radiological assessment of atrophy, which is typically based on the evaluation of the cerebrospinal fluid spaces.

OBJETIVO: Analisar, quantitativamente, o volume cerebral de idosos em uma amostra de base populacional em São Paulo. MATERIAIS E MÉTODOS: O estudo é uma avaliação radiológica e análise quantitativa baseada em voxel com alinhamento de superfície de 525 imagens de ressonância magnética de participantes de uma coorte de idosos (SABE - Saúde, Bem-estar e Envelhecimento) em São Paulo, Brasil, com idades de 60 a 103 anos, dos dois sexos. RESULTADOS: Observamos redução média do volume cerebral total de 2,4% por década após os 60 anos de idade. A redução de volume ocorreu na substância cinzenta e na substância branca com a idade. A relação entre volume cerebral intracraniano e volume cerebral total diferiu entre homens e mulheres. CONCLUSÃO: Nós reproduzimos os achados de estudos prévios em populações americanas e europeias. A relação entre volume intracraniano e volume cerebral é maior em homens, o que pode representar fonte de viés na avaliação de atrofia radiológica convencional, já que essa avaliação é usualmente baseada em análise de espaços liquóricos intracranianos.

Spectrum of central nervous system involvement in rheumatic diseases: pictorial essay.

The rheumatic diseases, which include systemic lupus erythematosus, rheumatoid arthritis, Behçet's disease, scleroderma, and ankylosing spondylitis, are characterized by involvement of connective tissue, with multiple manifestations. In those diseases, there can be involvement of the peripheral or central nervous system, and that involvement can be primary, presenting as a major feature of the clinical presentation, or secondary, as an effect of the drugs used in order to control a given disease or its complications. Knowledge of the wide variety of imaging findings is crucial to the diagnosis of a rheumatic disease, especially in the early stages, enabling effective treatment and minimizing disability. This pictorial essay, presenting cases from the records of two tertiary teaching hospitals, encompasses cases of patients diagnosed with rheumatic disease and illustrates the neuroradiological findings on magnetic resonance imaging and computed tomography, in order to emphasize the importance of these methods for properly diagnosing rheumatic diseases.

Magnetic resonance imaging findings in central nervous system cryptococcosis: comparison between immunocompetent and immunocompromised patients.

OBJECTIVE: To assess the magnetic resonance imaging (MRI) patterns associated with central nervous system infection with Cryptococcus sp. in relation to patient immune status. MATERIALS AND METHODS: This was a retrospective study of MRI data for 19 patients with neurocryptococcosis who underwent the examination between January 2000 and March 2014. The MRI characteristics examined included lesion topography, aspects of diffusion, T1-weighted images, T2-weighted images, and contrast enhancement patterns. RESULTS: In all cases, cryptococcal infection was confirmed by cerebrospinal fluid analysis. Of the 19 patients, 10 were immunocompromised and 9 were immunocompetent. Abnormal imaging patterns occurred alone or in conjunction with other manifestations. The imaging patterns found in immunocompromised patients included the following: leptomeningeal enhancement, in 6; pachymeningeal enhancement, in 3 (due to intracranial hypotension in 2); perivascular space involvement, in 4; granulomas, in 2; hydrocephalus, in 2; miliary nodules, in 1; and plexitis, in 1. In immunocompetent patients, the following imaging patterns were observed: leptomeningeal enhancement, in 5; perivascular space involvement, in 3; granulomas, in 3; cryptococcoma, in 1; ventriculitis, in 1; and hydrocephalus, in 1. In 2 immunocompetent patients, diffusion-weighted imaging showed diffusion restriction in cerebral cryptococcal granuloma. CONCLUSION: In both groups, the most common imaging finding was leptomeningeal enhancement, followed by dilatation of perivascular spaces with the presence of mucoid material. Rare presentations, such as miliary nodules, plexitis, ventriculitis, and pachymeningeal enhancement, were also observed. None of the imaging patterns common to immunocompetent and immunocompromised patients differed significantly in frequency between them.

OBJETIVO: Avaliar os padrões de ressonância magnética (RM) associados à infecção do sistema nervoso central por Cryptococcus sp. em relação ao status imunológico dos pacientes. MATERIAIS E MÉTODOS: Dados de RM de 19 casos de neurocriptococose foram analisados retrospectivamente de janeiro de 2000 a março de 2014. As características de RM examinadas incluíram: sítio da lesão, aspectos em difusão, imagens ponderadas em T1 e T2 e padrões de realce pelo contraste. RESULTADOS: A infecção por Cryptococcus sp. foi confirmada pela análise do liquor em todos os casos. Dos 19 pacientes, 10 eram imunossuprimidos e 9 eram imunocompetentes. Os padrões de imagem anormais ocorreram isoladamente ou em associação com outras manifestações. Os padrões de imagem encontrados nos pacientes imunossuprimidos incluíram: realce leptomeníngeo (n = 6), realce paquimeníngeo (n = 3; 2 devidos a hipotensão intracraniana), envolvimento do espaço perivascular (n = 4), granulomas (n = 2), hidrocefalia (n = 2), nódulos miliares (n = 1) e plexite (n = 1). Em pacientes imunocompetentes, os padrões de imagem incluíram: realce leptomeníngeo (n = 5), envolvimento do espaço perivascular (n = 3), granulomas (n = 3), criptococoma (n = 1), ventriculite (n = 1) e hidrocefalia (n = 1). As sequências ponderadas em difusão mostraram restrição em 2 pacientes imunocompetentes com granulomas intracerebrais por criptococose. CONCLUSÃO: O achado mais comum de imagem em ambos os grupos foi realce leptomeníngeo, seguido de dilatação dos espaços perivasculares pela presença do material mucoide. Apresentações raras como nódulos miliares, plexite, ventriculite e realce paquimeníngeo foram também observadas. Nenhum dos padrões de imagem comuns aos pacientes imunocompetentes e imunossuprimidos diferiu significativamente em frequência entre eles.

Right Cardiac Chambers Involvement by a Malignant Testicular Germ Cell Tumor: An Imaging-pathologic Correlation.

The cardiac chamber's involvement with neoplastic embolism has been rarely reported; it is mostly associated with gastric, breast, lung, liver, and prostate cancers, and usually affects the pulmonary arteries. This paper reports a case of a 31-year-old man with a malignant testicular germ cell tumor who presented with multiple episodes of pulmonary thromboembolism and died of sudden respiratory failure 1 year after the initial diagnosis. Death was attributed to massive pulmonary embolism and pulmonary infarction associated with a neoplastic thrombus that extended from the gonadal veins to pulmonary arteries. A postmortem computerized tomographic angiography and autopsy confirmed this finding.