RESUMO
A wide range of neurological manifestations have been associated with the development of COVID-19 following SARS-CoV-2 infection. However, the etiology of the neurological symptomatology is still largely unexplored. Here, we used state-of-the-art multiplexed immunostaining of human brains (n = 6 COVID-19, median age = 69.5 years; n = 7 control, median age = 68 years) and demonstrated that expression of the SARS-CoV-2 receptor ACE2 is restricted to a subset of neurovascular pericytes. Strikingly, neurological symptoms were exclusive to, and ubiquitous in, patients that exhibited moderate to high ACE2 expression in perivascular cells. Viral dsRNA was identified in the vascular wall and paralleled by perivascular inflammation, as signified by T cell and macrophage infiltration. Furthermore, fibrinogen leakage indicated compromised integrity of the blood-brain barrier. Notably, cerebrospinal fluid from additional 16 individuals (n = 8 COVID-19, median age = 67 years; n = 8 control, median age = 69.5 years) exhibited significantly lower levels of the pericyte marker PDGFRß in SARS-CoV-2-infected cases, indicative of disrupted pericyte homeostasis. We conclude that pericyte infection by SARS-CoV-2 underlies virus entry into the privileged central nervous system space, as well as neurological symptomatology due to perivascular inflammation and a locally compromised blood-brain barrier.
Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , Encéfalo/virologia , COVID-19/fisiopatologia , Encefalite Viral/virologia , Pericitos/virologia , Enzima de Conversão de Angiotensina 2/genética , Animais , Barreira Hematoencefálica , Encéfalo/patologia , COVID-19/etiologia , Estudos de Casos e Controles , Encefalite Viral/patologia , Fibrinogênio/metabolismo , Humanos , Imuno-Histoquímica/métodos , Camundongos , Pericitos/metabolismo , Pericitos/patologia , Receptor beta de Fator de Crescimento Derivado de Plaquetas/líquido cefalorraquidianoRESUMO
BACKGROUND: There are few studies on the locus coeruleus (LC) in frontotemporal lobar degeneration (FTLD) and the potential differences in the LC related to the underlying proteinopathy. OBJECTIVE: The aim of this study was to investigate the LC in FTLD subgroups. METHODS: Neuropathological cases diagnosed with FTLD were included. The subgroups consisted of FTLD with tau, transactive response DNA-binding protein 43 (TDP) and fused in sarcoma (FUS). Micro- and macroscopical degeneration of the LC were assessed with respect to the number of neurons and the degree of depigmentation. A group of cognitively healthy subjects and a group with vascular cognitive impairment (VCI) served as comparison groups. RESULTS: A total of 85 FTLD cases were included, of which 44 had FTLD-TDP, 38 had FTLD-tau, and three had FTLD-FUS. The groups were compared with 25 VCI cases and 41 cognitively healthy control cases (Nâ=â151 for the entire study). All FTLD groups had a statistically higher microscopical degeneration of the LC compared to the controls, but the FTLD-tau group had greater micro- and macroscopical degeneration than the FTLD-TDP group. Age correlated positively with the LC score in the FTLD-tau group, but not in the FTLD-TDP group. CONCLUSION: A greater microscopical degeneration of the LC was observed in all FTLD cases compared to healthy controls and those with VCI. The LC degeneration was more severe in FTLD-tau than in FTLD-TDP. The macroscopically differential degeneration of the LC in FTLD subgroups may facilitate differential diagnostics, potentially with imaging.
Assuntos
Demência Frontotemporal , Degeneração Lobar Frontotemporal , Proteínas de Ligação a DNA/metabolismo , Demência Frontotemporal/psicologia , Degeneração Lobar Frontotemporal/diagnóstico , Humanos , Locus Cerúleo/patologiaRESUMO
The preferred management of a cardiac mass remains controversial, but it often includes open-chest surgical excision to obtain an adequate tissue sample for histological workup. We herein report a less invasive approach in which an accurate and timely cytological diagnosis of pericardial angiosarcoma was reached by studying a CT-guided fine-needle aspiration cell block. The cell block showed proliferation of atypical cells with occasional mitotic figures, vasoformative features, and immunoreactivity to WT1, vimentin, CD31, CD34, ERG, and Ki67. Recourse to fine-needle aspiration and cell block study is a valuable diagnostic approach to be considered when a cardiac mass is percutaneously accessible.
Assuntos
Neoplasias Cardíacas/diagnóstico , Hemangiossarcoma/diagnóstico , Pericárdio/patologia , Radiografia Intervencionista/métodos , Biomarcadores Tumorais/análise , Biópsia por Agulha Fina , Evolução Fatal , Feminino , Neoplasias Cardíacas/patologia , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND AND OBJECTIVE: Secondary amyloidosis (AA) is a rare complication of rheumatic diseases. OBJECTIVE: The aim of this study was to determine the frequency of symptomatic amyloidosis AA in patients with spondyloarthropathy. PATIENTS AND METHOD: Retrospective study (1984-2013). We reviewed the medical records of patients with spondyloarthropathy who had a histological diagnosis of amyloidosis AA (15 patients). RESULTS: We identified 1.125 patients with spondyloarthropathies. Fifteen (1.3%) patients with amyloidosis AA were recruited. It was suspected in 14 patients (93.3%) because of nephrotic syndrome in most of them: 14 were symptomatic (93.3%): 5 (33.3%) ankylosing spondylitis (AS), 5 (33.3%) spondylitis associated with inflammatory bowel diseases (IBD), 4 (26.7%) psoriatic arthritis, and one (6.7%) reactive arthritis. The mean disease duration was 23.9 years. Mortality after one and 5 years of follow-up was 30 and 50% respectively. CONCLUSIONS: The frequency of clinical amyloidosis AA in our patients was 1.3%. There was a marked male predominance, with AS or IBD. Clinical amyloidosis was diagnosed at a relatively late stage in spondyloarthropathy.
Assuntos
Amiloidose/etiologia , Espondiloartropatias/complicações , Adulto , Amiloidose/diagnóstico , Amiloidose/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
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