RESUMO
Disposition of amyloid ß (Aß) into the perivascular space of the cerebral cortex has been recently suggested as a major source of its clearance, and its disturbance may be involved in the pathogenesis of cerebral amyloid angiopathy and Alzheimer's disease. Here, we explored the in vivo dynamics of Aß in the perivascular space of anesthetized mice. Live images were obtained with two-photon microscopy through a closed cranial window. Either fluorescent-dye-labeled Aß oligomers prepared freshly or Aß fibrils after 6 days of incubation at 37 °C were placed over the cerebral cortex. Accumulation of Aß was observed in the localized perivascular space of the penetrating arteries and veins. Transportation of the accumulated Aß along the vessels was slow and associated with changes in shape. Aß oligomers were transported smoothly and separately, whereas Aß fibrils formed a mass and moved slowly. Parenchymal accumulation of Aß oligomers, as well as Aß fibrils along capillaries, increased gradually. In conclusion, we confirmed Aß transportation between the cortical surface and the deeper parenchyma through the perivascular space that may be affected by the peptide polymerization. Facilitation of Aß excretion through the system can be a key target in treating Alzheimer's disease.
Assuntos
Doença de Alzheimer , Angiopatia Amiloide Cerebral , Doença de Alzheimer/patologia , Amiloide , Peptídeos beta-Amiloides/metabolismo , Animais , Encéfalo/metabolismo , Angiopatia Amiloide Cerebral/patologia , Córtex Cerebral/metabolismo , Camundongos , PolimerizaçãoRESUMO
Eosinophilic granulomatosis with polyangiitis (EGPA) is often associated with peripheral neuropathy, but reports of central nervous system involvement are quite rare. We herein report a patient with EGPA first identified as having hypereosinophilia who later developed asthma, eosinophilic otitis media, sinusitis, and hemorrhagic colitis. She subsequently developed hemiparesis. Head magnetic resonance imaging revealed multiple cerebral infarctions with subcortical and subarachnoid hemorrhaging colocalized at the bilateral border zone areas. She was diagnosed with EGPA-induced stroke and successfully treated with oral prednisolone. Inflammation in the small cerebral arteries in EGPA may induce bilateral border zone infarction with colocalizing subcortical and subarachnoid hemorrhaging.
Assuntos
Síndrome de Churg-Strauss , Eosinofilia , Granulomatose com Poliangiite , Hemorragia Subaracnóidea , Infarto Cerebral/complicações , Infarto Cerebral/etiologia , Síndrome de Churg-Strauss/complicações , Síndrome de Churg-Strauss/diagnóstico , Eosinofilia/complicações , Eosinofilia/diagnóstico por imagem , Feminino , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/diagnóstico por imagem , Humanos , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/diagnóstico por imagemRESUMO
BACKGROUND: In patients with multiple sclerosis (MS), development of hepatic injury has been sporadically reported after methylprednisolone (MP) pulse therapy. Some studies suggest autoimmune hepatitis, while other studies reported direct hepatotoxicity as a cause for hepatic injury. Here, we studied the pathological mechanism of such liver injury in patients with MS. METHODS: From 2005 to 2016, eight patients with MS developed liver injury after MP pulse therapy. Their average age was 38 years (range: 28-49 years, all female). Autoimmune antibodies were measured and a liver biopsy was performed in seven patients. RESULTS: Liver injury developed within two weeks in two patients and later (30-90 days after MP) in six patients. No hepatitis-related autoantibody or hepatitis virus were found. All cases were classified as hepatocellular injury and none as cholestatic or mixed. A liver biopsy in five cases revealed centrilobular necrosis with lobular infiltrates of inflammatory cells, suggesting drug-induced acute hepatitis. The biopsy findings in another case suggested a residual stage of acute hepatitis. Only one patient showed portal expansion with periportal fibrosis, suggesting autoimmune hepatitis. All patients recovered spontaneously or with only hepatoprotective drugs, although one patient with possible autoimmune hepatitis recovered slowly. CONCLUSION: Liver injury develops usually later than two weeks after MP treatment. The prognosis is good in most cases and rarely autoimmune hepatitis may be involved.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Hepatite/etiologia , Fatores Imunológicos/efeitos adversos , Metilprednisolona/efeitos adversos , Esclerose Múltipla/tratamento farmacológico , Adulto , Feminino , Hepatite Autoimune/etiologia , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/toxicidade , Metilprednisolona/administração & dosagem , Metilprednisolona/toxicidade , Pessoa de Meia-IdadeAssuntos
Encefalopatias/diagnóstico , Intoxicação por Monóxido de Carbono/diagnóstico , Transplante de Rim , Idoso , Encefalopatias/fisiopatologia , Encefalopatias/terapia , Intoxicação por Monóxido de Carbono/fisiopatologia , Intoxicação por Monóxido de Carbono/terapia , Diagnóstico Tardio , Diagnóstico Diferencial , Humanos , Oxigenoterapia Hiperbárica , Imunossupressores/administração & dosagem , Masculino , Valor Preditivo dos Testes , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do TratamentoRESUMO
Pulmonary arteriovenous fistula (PAVF), a vessel malformation connecting the pulmonary circulation to the systemic circulation while bypassing the pulmonary capillaries, can cause paradoxical cerebral infarction. It is often associated with hereditary hemorrhagic telangiectasia (HHT), a genetic disease characterized by multiple dermal, mucosal, and visceral telangiectasia causing recurrent bleeding. Paradoxical cerebral embolism caused by PAVF without HHT is rare. Here, we report a patient with isolated PAVF who experienced an ischemic stroke caused by a paradoxical embolism from deep venous thrombosis; the patient was successfully treated with recombinant tissue plasminogen activator. She presented with a decrease in arterial oxygen saturation to 91%, and lung disease was suspected. A PAVF was subsequently found in the right S6 region using contrast computed tomography. Interventional radiologists successfully occluded the shunt using 6 microcoils. PAVF should be considered when determining the pathogenesis of cerebral ischemia in patients with hypoxia, which can be the only symptom of PAVF.
Assuntos
Fístula Arteriovenosa/complicações , Embolia Paradoxal/tratamento farmacológico , Fibrinolíticos/administração & dosagem , Embolia Intracraniana/tratamento farmacológico , Artéria Pulmonar/anormalidades , Veias Pulmonares/anormalidades , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/administração & dosagem , Trombose Venosa/complicações , Idoso de 80 Anos ou mais , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/terapia , Angiografia Cerebral/métodos , Angiografia por Tomografia Computadorizada , Imagem de Difusão por Ressonância Magnética , Embolia Paradoxal/diagnóstico por imagem , Embolia Paradoxal/etiologia , Embolização Terapêutica/instrumentação , Inibidores do Fator Xa/uso terapêutico , Feminino , Humanos , Embolia Intracraniana/diagnóstico , Embolia Intracraniana/diagnóstico por imagem , Angiografia por Ressonância Magnética , Artéria Pulmonar/diagnóstico por imagem , Veias Pulmonares/diagnóstico por imagem , Piridinas/uso terapêutico , Proteínas Recombinantes/administração & dosagem , Tiazóis/uso terapêutico , Resultado do Tratamento , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/tratamento farmacológicoRESUMO
Mild cognitive impairment (MCI) can include the transition from a normal state to dementia. To explore biomarkers for the development of dementia, we performed an 18-month follow-up study in 28 patients with amnestic MCI. Amyloid deposition was examined using PiB PET, and cerebral blood flow (CBF) was examined using SPECT. Cognitive function was periodically assessed. The rate of conversion to dementia was higher in the PiB-positive/equivocal group (74%) than in the PiB-negative group (33%) (p = 0.041). Perfusion SPECT was performed in 16 patients. MCI patients with an AD-characteristic pattern of reduced CBF had a higher PiB-positive/equivocal rate (82%) than those with a non-AD pattern (20%) (p = 0.018), and patients with an AD pattern had a higher conversion rate (82%) than those with a non-AD pattern (40%) (p = 0.094). Clinically, all PiB-positive converters were diagnosed as having Alzheimer's disease (AD), whereas PiB-negative converters were thought to have some form of dementia other than AD. Amyloid PET is useful for predicting conversion to AD in MCI patients. A pattern analysis of perfusion SPECT findings might also be helpful for predicting conversion to AD, but with a lower specificity.