RESUMO
Inflammatory pituitary lesions account for 1.8% of all specimens from the German Pituitary Tumor Registry. They occure in 0.5% of the autoptical specimens and in 2.2% of the surgical cases. Women are significantly more often affected than men and are often younger when first diagnosed. In general, primary and secondary inflammation can be distinguished, with secondary types occurring more frequently (75.1%) than idiopathic inflammatory lesions (15.4%). In primary inflammation, the lymphocytic type is more common (88.5%) than the granulomatous type of hypophysitis (11.5%). The most common causes of secondary inflammation are Rathke's cleft cysts (48.6%), followed by tumors (17.4%) such as the craniopharyngioma (9.1%), adenoma (5.5%) or germinoma (2.0%). More causes are tumor-like lesions (7.1%) such as xanthogranuloma (3.5%) or Langerhans histiocytosis (3.5%), abscesses (5.5%), generalized infections (5.1%), spreaded inflammations (4.7%) and previous surgeries (4.0%). In 1.6% of all specimens the reason for the inflammation remains unclear. The described classification of hypophysitis is important for specific treatment planning after surgery.
Assuntos
Cistos do Sistema Nervoso Central , Craniofaringioma , Doenças da Hipófise , Neoplasias Hipofisárias , Feminino , Humanos , Masculino , Doenças da Hipófise/epidemiologia , HipófiseRESUMO
This article describes a hantavirus-associated pronounced myositis as a rare differential diagnosis to polymyositis. The literature on the pathogenesis of hantavirus disease discusses less a direct viral cytopathology but more a secondary immune dysregulation with induction of a capillary leak. This article describes for the first time a case of successful treatment of protracted hantavirus myositis using high-dose glucocorticoids and cyclophosphamide, followed by ciclosporin and MTX.
Assuntos
Miosite , Polimiosite , Ciclofosfamida/uso terapêutico , Ciclosporina/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Miosite/diagnóstico , Polimiosite/diagnóstico , Polimiosite/tratamento farmacológico , Polimiosite/patologiaRESUMO
The health effects of coronavirus disease 2019 (COVID-19) caused by the infection of SARS-CoV2 (severe acute respiratory syndrome coronavirus 2) are becoming increasingly clear as the pandemic spreads. In addition to the lungs, other organs are also affected, which can significantly influence morbidity and mortality. In particular, neurological symptoms involving the central nervous system can lead to acute or long-term consequences. The mechanisms of this neuropathogenesis of SARS-CoV2 infection and its relation to acute and chronic neurological symptoms are the subject of current studies investigating a potential direct and indirect viral infection of the nervous system. The following review summarizes the current status of neuropathological manifestations, molecular pathogenesis, possible infection pathways in the nervous system, and systemic effects. In addition, an overview of the Germany-wide CNS-COVID19 registry and collaborations is presented, which should contribute to a better understanding of the neurological symptoms of COVID-19.
Assuntos
COVID-19 , Alemanha , Humanos , Pandemias , Sistema Nervoso Periférico , SARS-CoV-2RESUMO
AIMS: In the search for blood-based biomarkers of neurodegenerative diseases, we characterized the concentration of total prion protein (t-PrP) in the plasma of neurodegenerative dementias. We aimed to assess its accuracy in this differential diagnostic context. METHODS: Plasma t-PrP was measured in 520 individuals including healthy controls (HC) and patients diagnosed with neurological disease control (ND), Alzheimer's disease (AD), sporadic Creutzfeldt-Jakob disease (sCJD), frontotemporal dementia (FTD), Lewy body dementia (LBD) and vascular dementia (VaD). Additionally, t-PrP was quantified in genetic prion diseases and iatrogenic CJD. The accuracy of t-PrP discriminating the diagnostic groups was evaluated and correlated with demographic, genetic and clinical data in prion diseases. Markers of blood-brain barrier impairment were investigated in sCJD brains. RESULTS: Compared to HC and ND, elevated plasma t-PrP concentrations were detected in sCJD, followed by FTD, AD, VaD and LBD. In sCJD, t-PrP was associated neither with age nor sex, but with codon 129 PRNP genotype. Plasma t-PrP concentrations correlated with cerebrospinal fluid (CSF) markers of neuro-axonal damage, but not with CSF t-PrP. In genetic prion diseases, plasma t-PrP was elevated in all type of mutations investigated. In sCJD brain tissue, extravasation of immunoglobulin G and the presence of swollen astrocytic end-feet around the vessels suggested leakage of blood-brain barrier as a potential source of increased plasma t-PrP. CONCLUSIONS: Plasma t-PrP is elevated in prion diseases regardless of aetiology. This pilot study opens the possibility to consider plasma t-PrP as a promising blood-based biomarker in the diagnostic of prion disease.
Assuntos
Biomarcadores/sangue , Demência/diagnóstico , Doenças Neurodegenerativas/diagnóstico , Doenças Priônicas/diagnóstico , Proteínas Priônicas/sangue , Adulto , Idoso , Demência/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Neurodegenerativas/sangue , Doenças Priônicas/sangueRESUMO
Serum antibodies against amyloid-ß peptide (Aß) in humans with or without diagnosis of Alzheimer's disease (AD) indicate the possibility of immune responses against brain antigens. In an unbiased screening for antibodies directed against brain proteins, we found in AD patients high serum levels of antibodies against the neuronal cytoskeletal protein ankyrin G (ankG); these correlated with slower rates of cognitive decline. Neuronal expression of ankG was higher in AD brains than in nondemented age-matched healthy control subjects. AnkG was present in exosomal vesicles, and it accumulated in ß-amyloid plaques. Active immunization with ankG of arcAß transgenic mice reduced brain ß-amyloid pathology and increased brain levels of soluble Aß(42). AnkG immunization induced a reduction in ß-amyloid pathology, also in Swedish transgenic mice(.) Anti-ankG monoclonal antibodies reduced Aß-induced loss of dendritic spines in hippocampal ArcAß organotypic cultures. Together, these data established a role for ankG in the human adaptive immune response against resident brain proteins, and they show that ankG immunization reduces brain ß-amyloid and its related neuropathology.
Assuntos
Doença de Alzheimer/imunologia , Doença de Alzheimer/prevenção & controle , Anquirinas/imunologia , Encéfalo/patologia , Vacinação , Doença de Alzheimer/sangue , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/toxicidade , Animais , Anquirinas/metabolismo , Anticorpos/sangue , Anticorpos Monoclonais/farmacologia , Encéfalo/metabolismo , Células Cultivadas , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Humanos , Camundongos , Camundongos Transgênicos , Neurônios/citologia , Fragmentos de Peptídeos/metabolismo , Placa Amiloide/metabolismoRESUMO
BACKGROUND: Primary angiitis of the central nervous system (PACNS) is a rare but serious condition. A fraction of patients suffering from PACNS concurrently exhibit pronounced cerebral amyloid angiopathy (CAA) which is characterized by deposits of amyloid-ß (Aß) in and around the walls of small and medium-sized arteries of the brain. PACNS with CAA has been identified as a distinct disease entity, termed Aß-related angiitis (ABRA). Evidence points to an immune reaction to vessel wall Aß as the trigger of vasculitis. OBJECTIVE: To investigate whether the inflammatory response to Aß has (1) any effect on the status of immune activation in the brain parenchyma and (2) leads to clearance of Aß from brain parenchyma. METHODS: We studied immune activation and Aß load by quantitative immunohistochemical analysis in brain parenchyma adjacent to affected vessels in 11 ABRA patients and 10 matched CAA controls. RESULTS: ABRA patients showed significantly increased immune activation and decreased Aß loads in the brain parenchyma adjacent to affected vessels. CONCLUSION: Our results are in line with the hypothesis of ABRA being the result of an excessive immune response to Aß and show that this can lead to enhanced clearance of Aß from the brain parenchyma by immune-mediated mechanisms.
Assuntos
Peptídeos beta-Amiloides/imunologia , Encéfalo/imunologia , Encéfalo/patologia , Vasculite do Sistema Nervoso Central/imunologia , Vasculite do Sistema Nervoso Central/patologia , Idoso , Peptídeos beta-Amiloides/análise , Estudos de Casos e Controles , Angiopatia Amiloide Cerebral/imunologia , Angiopatia Amiloide Cerebral/patologia , Feminino , Humanos , Imuno-Histoquímica , Ativação de Macrófagos , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Placa Amiloide/imunologia , Placa Amiloide/patologiaRESUMO
Sporadic Alzheimer's disease (SAD) is the most common form of dementia, and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most frequent hereditary ischemic small vessel disease of the brain. Relevant biomarkers or specific metabolic signatures could provide powerful tools to manage these diseases. Therefore, the main goal of this study was to compare the postmortem frontal cortex gray matter, white matter and cerebrospinal fluid (CSF) between a cognitively healthy group and CADASIL and SAD groups. We evaluated 352 individual lipids, belonging to 13 lipid classes/subclasses, using mass spectrometry, and the lipid profiles were subjected to multivariate analysis to discriminate between the dementia groups (CADASIL and SAD) and healthy controls. The main lipid molecular species showing greater discrimination by partial least squares-discriminant analysis (PLS-DA) and a higher significance multivariate correlation (sMC) index were as follows: phosphatidylserine (PS) PS(44:7) and lysophosphatidylethanolamine (LPE) LPE(18:2) in gray matter (GM); phosphatidylethanolamine (PE) PE(32:2) and phosphatidylcholine PC PC(44:6) in white matter (WM), and ether PE (ePE) ePE(38:2) and ether PC (ePC) ePC(34:3) in CSF. Common phospholipid molecular species were obtained in both dementias, such as PS(44:7) and lyso PC (LPC) LPC(22:5) in GM, PE(32:2) in WM and phosphatidic acid (PA) PA(38:5) and PC(42:7) in CFS. Our exploratory study suggests that phospholipids (PLs) involved in neurotransmission alteration, connectivity impairment and inflammation response in GM, WM and CSF are a transversal phenomenon affecting dementias such as CADASIL and SAD independent of the etiopathogenesis, thus providing a possible common prodromal phospholipidic biomarker of dementia.
Assuntos
Doença de Alzheimer/metabolismo , CADASIL/metabolismo , Lobo Frontal/metabolismo , Substância Cinzenta/metabolismo , Tecido Parenquimatoso/metabolismo , Fosfolipídeos/metabolismo , Substância Branca/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/patologia , Autopsia , Biomarcadores/análise , CADASIL/diagnóstico , CADASIL/patologia , Estudos de Casos e Controles , Análise Discriminante , Feminino , Lobo Frontal/patologia , Substância Cinzenta/patologia , Humanos , Análise dos Mínimos Quadrados , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Tecido Parenquimatoso/patologia , Fosfolipídeos/química , Fosfolipídeos/classificação , Fosfolipídeos/isolamento & purificação , Substância Branca/patologiaRESUMO
In scrapie-infected mice, prions are found associated with splenic but not circulating B and T lymphocytes and in the stroma, which contains follicular dendritic cells (FDCs). Formation and maintenance of mature FDCs require the presence of B cells expressing membrane-bound lymphotoxin-alpha/beta. Treatment of mice with soluble lymphotoxin-beta receptor results in the disappearance of mature FDCs from the spleen. We show that this treatment abolishes splenic prion accumulation and retards neuroinvasion after intraperitoneal scrapie inoculation. These data provide evidence that FDCs are the principal sites for prion replication in the spleen.
Assuntos
Células Dendríticas Foliculares/patologia , Células Dendríticas Foliculares/virologia , Proteínas PrPSc/biossíntese , Baço/patologia , Baço/virologia , Replicação Viral/imunologia , Animais , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Células Dendríticas Foliculares/metabolismo , Imunoglobulinas/genética , Receptor beta de Linfotoxina , Linfotoxina-alfa/antagonistas & inibidores , Linfotoxina-alfa/genética , Linfotoxina-alfa/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos SCID , Proteínas PrPSc/administração & dosagem , Receptores do Fator de Necrose Tumoral/antagonistas & inibidores , Receptores do Fator de Necrose Tumoral/genética , Receptores do Fator de Necrose Tumoral/imunologia , Proteínas Recombinantes de Fusão/administração & dosagem , Scrapie/imunologia , Scrapie/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Baço/imunologia , Baço/metabolismo , Replicação Viral/genéticaRESUMO
The objective of this study was to investigate the therapeutic effects of doxorubicin bound to polysorbate-coated nanoparticles that had previously been shown to significantly enhance survival in the orthotopic rat 101/8 glioblastoma model. Tumor-bearing animals were subjected to chemotherapy using doxorubicin in solution (Dox-sol) or doxorubicin bound to polysorbate 80-coated poly(butyl cyanoacrylate) nanoparticles (Dox-np) injected intravenously on Days 2, 5 and 8 post tumor implantation. The antitumor effect was assessed on Days 10, 14 and 18 post tumor implantation. Tumors showed signs of malignancy including invasion of brain tissue, brisk mitotic activity, microvascular proliferation, necrosis and increased proliferation resembling human glioblastoma. Dox-np produced a considerably more pronounced antitumor effect exhibited as a reduced tumor size, lower proliferation, and a decreased necrotic area compared to Dox-sol and to untreated control groups. A drastic effect of Dox-np on vascularization indicated an antiangiogenic mode of action.
Assuntos
Inibidores da Angiogênese/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos , Glioblastoma/tratamento farmacológico , Animais , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Glioblastoma/patologia , Imuno-Histoquímica , Masculino , Nanopartículas , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/patologia , Polissorbatos/administração & dosagem , Ratos , Ratos WistarRESUMO
Transmissible spongiform encephalopathies are commonly propagated by extracerebral inoculation of the infectious agent. Indirect evidence suggests that entry into the central nervous system occurs via the peripheral nervous system. Here we have investigated the role of the sympathetic nervous system in prion neuroinvasion. Following intraperitoneal prion inoculation, chemical or immunological sympathectomy delayed or prevented scrapie. Prion titers in spinal cords were drastically reduced at early time points after inoculation. Instead, keratin 14-NGF transgenic mice, whose lymphoid organs are hyperinnervated by sympathetic nerves, showed reduction in scrapie incubation time and, unexpectedly, much higher titers of prion infectivity in spleens. We conclude that sympathetic innervation of lymphoid organs is rate limiting for prion neuroinvasion and that splenic sympathetic nerves may act as extracerebral prion reservoirs.