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2.
Top Magn Reson Imaging ; 28(4): 213-224, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31385901

RESUMO

Task-based functional magnetic resonance imaging (fMRI) for the presurgical assessment of eloquent cortex is increasingly relied upon by surgeons, neurologists, and radiologists. The utility of fMRI stems from the lack of correlation between topographic anatomy and functional anatomy. fMRI can noninvasively reveal the functional anatomy of a given individual thereby allowing the surgeon to choose the most appropriate surgical trajectory, attain the most complete resection, and offer the best chance of preserving function. This dissociation between function and topography is even more critical to understand when disease distorts normal anatomic relations and when chronic evolution of pathology leads to reorganization of cortical function as can be seen with seizures or slow growing tumors. fMRI can demonstrate the functional anatomy of language, motor, vision, and memory systems. Accurate interpretation not only requires knowledge of the expected patterns of activations in the regions of interest but also demands an understanding of the many adjacent "bystander" activations that represent participatory neural activity but not the eloquent region in question. In addition, fMRI interpretation requires an understanding of the limitations of this technique when expected activity is either missing or seemingly displaced in location.


Assuntos
Encefalopatias/diagnóstico por imagem , Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Encéfalo/fisiopatologia , Encéfalo/cirurgia , Encefalopatias/patologia , Encefalopatias/fisiopatologia , Encefalopatias/cirurgia , Humanos , Linguagem , Cuidados Pré-Operatórios/métodos
3.
J Zoo Wildl Med ; 50(2): 482-486, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31260220

RESUMO

A 0.5 kg, 5-yr-old male bearded dragon (Pogona vitticeps) presented with a 2-mo history of lethargy, anorexia, and impaired locomotion. Upon physical examination, bradyarrhythmia (heart rate: 20 beats/min) and balance disorders were noted. Electrocardiography revealed a first-degree atrioventricular block (P-R interval: 360 ms). On echocardiography, all cardiac chambers were slightly above normal ranges. Complete blood count, blood biochemistry, and T4 were unremarkable except for mildly elevated aspartate aminotransferase. Adenovirus testing was negative by polymerase chain reaction. Following euthanasia, necropsy revealed marked thickening of the arterial trunks and histopathology confirmed multifocal atherosclerosis of efferent heart vessels, arteriosclerosis of cerebral arterioles, and multifocal spongiosis of brain tissue, more pronounced in the optic chiasma. Owing to its severity, atherosclerosis may have contributed to chronic arterial hypertension with damages to the heart, brain vessels, and brain tissue-optic chiasma.


Assuntos
Aterosclerose/veterinária , Bloqueio Atrioventricular/veterinária , Encefalopatias/veterinária , Cardiopatias/veterinária , Hipertensão/veterinária , Lagartos , Animais , Aterosclerose/patologia , Bloqueio Atrioventricular/patologia , Encefalopatias/etiologia , Encefalopatias/patologia , Cardiopatias/etiologia , Cardiopatias/patologia , Hipertensão/complicações , Masculino
4.
Front Neurol Neurosci ; 44: 108-117, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31220831

RESUMO

The representation of cognitive function in the cerebral cortex has a long and cherished history, but much evidence also supports a critical role of subcortical structures in the operations of cognition. The idea of subcortical dementia, first proposed in 1932 and substantially expanded in the 1970s, is the most prominent formulation intended to capture the phenomenology of cognitive impairment attributable to subcortical involvement. Despite criticism highlighting its imprecision, subcortical dementia has endured as a useful general concept assisting the classification of dementia syndromes based on the primary site(s) of neuropathology. As neuroscientific knowledge expanded with the advent of modern structural and functional neuroimaging, a more detailed understanding of the contributions of specific subcortical regions emerged, such that the cognitive affiliations of the basal ganglia, thalamus, cerebellum, brainstem, and white matter are all better defined. Important advances have been made by the study of both neurodegenerative diseases and focal lesions. Today, the complex admixture of cortical and subcortical foundations of cognition is increasingly well appreciated, and has been conceptually organized within the broadly inclusive notion of distributed neural networks. These networks are thought to integrate cortical and subcortical gray and white matter structures throughout the brain into functional neuronal ensembles subserving various domains of cognition. In this light, specific disorders of subcortical regions produce cognitive sequelae that can be usefully analyzed within the context of networks that involve key cortical regions as well. The study of subcortical contributions to cognition has been highly informative in expanding neurobehavioral thinking to include regions beyond the cerebral cortex, adding nuance and sophistication to the conceptualization of brain-behavior relationships.


Assuntos
Encefalopatias/história , Cognição/fisiologia , Disfunção Cognitiva/história , Função Executiva/fisiologia , Encéfalo/patologia , Encefalopatias/patologia , Disfunção Cognitiva/diagnóstico , História do Século XIX , História do Século XX , Humanos , Imagem por Ressonância Magnética/história , Vias Neurais/patologia
5.
Eur J Radiol ; 116: 152-159, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31153558

RESUMO

BACKGROUND AND PURPOSE: Periventricular pseudocysts (PVPCs) are cystic cavities originating from the germinal matrix. The effects of PVPCs on the development of white matter (WM) in neonates remain unclear. This study aimed to characterise WM microstructural variations in neonates with PVPCs with and without additional abnormities on MRI. MATERIALS AND METHODS: Neonates with PVPCs and controls with no MRI abnormalities were retrospectively enrolled. Test subjects were divided into groups 1 (isolated PVPCs) and 2 (PVPCs with additional MRI abnormalities). The PVPC MRI features collected included lateralisation, locularity, anatomic location, and the maximum anteroposterior diameter. Diffusion tensor imaging (DTI)-derived fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) were compared between the PVPC and control groups using tract-based spatial statistics. RESULTS: Thirty-eight neonates with PVPCs and 60 controls were enrolled. Groups 1 and 2 contained 15 and 23 subjects, respectively. The additional MRI findings in group 2 included intracranial haemorrhage, punctate WM lesions, hypoxic-ischaemic encephalopathy, and acute cerebral infarction. No significant differences were found in PVPC MRI features between the 2 test groups. Compared to controls, no significant changes in DTI metrics were observed in group 1 neonates; whereas extensive WM regions with decreased FA, increased RD, and unchanged/increased AD were found in group 2. CONCLUSIONS: Isolated PVPCs are not independently correlated with WM microstructural variations in neonates. This result provides further evidence for supporting the benign outcome of fetuses with isolated PVPCs.


Assuntos
Encefalopatias/patologia , Cistos/patologia , Substância Branca/patologia , Anisotropia , Encefalopatias/congênito , Estudos de Casos e Controles , Cistos/congênito , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Recém-Nascido , Masculino , Estudos Retrospectivos
6.
Adv Neurobiol ; 22: 19-49, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31073931

RESUMO

The brain is the most complex organ of the body, and many pathological processes underlying various brain disorders are poorly understood. Limited accessibility hinders observation of such processes in the in vivo brain, and experimental freedom is often insufficient to enable informative manipulations. In vitro preparations (brain slices or cultures of dissociated neurons) offer much better accessibility and reduced complexity and have yielded valuable new insights into various brain disorders. Both types of preparations have their advantages and limitations with regard to lifespan, preservation of in vivo brain structure, composition of cell types, and the link to behavioral outcome is often unclear in in vitro models. While these limitations hamper general usage of in vitro preparations to study, e.g., brain development, in vitro preparations are very useful to study neuronal and synaptic functioning under pathologic conditions. This chapter addresses several brain disorders, focusing on neuronal and synaptic functioning, as well as network aspects. Recent progress in the fields of brain circulation disorders, excitability disorders, and memory disorders will be discussed, as well as limitations of current in vitro models.


Assuntos
Encefalopatias/patologia , Técnicas In Vitro/métodos , Modelos Neurológicos , Neurônios/patologia , Encéfalo/patologia , Encefalopatias/fisiopatologia , Humanos , Rede Nervosa/patologia , Sinapses/patologia
7.
J Vet Diagn Invest ; 31(4): 581-584, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31122163

RESUMO

Sida carpinifolia is a small subshrub that is distributed throughout Brazil and is responsible for lysosomal storage disease and occasional reproductive problems in cattle, goats, equids, sheep, and deer. We describe herein the clinical, epidemiologic, and pathologic features of hydrallantois in 3 cows naturally poisoned by S. carpinifolia in Rio Grande do Sul State, Brazil. Clinically, all cows had marked abdominal distension and mild ataxia. After natural death or euthanasia, autopsies revealed that the abdominal distension in all 3 cases was caused by severe enlargement of the uterus, which contained 100-120 L of translucent fluid within the allantois, in addition to adventitial placentation. Microscopic evaluation of the placenta revealed marked diffuse edema, sometimes with a myxomatous appearance. Neurons in the cerebellum and obex were swollen, with mild-to-moderate cytoplasmic granular vacuolation. Histochemical examination with lectins ConA, WGA, and sWGA revealed mild-to-marked staining in the cytoplasm of neurons of the cerebellum and medulla at the level of the obex, indicating the occurrence of α-mannosidosis.


Assuntos
Alantoide/efeitos dos fármacos , Doenças dos Bovinos/induzido quimicamente , Malvaceae/toxicidade , Intoxicação por Plantas/veterinária , Alantoide/patologia , Animais , Encefalopatias/patologia , Encefalopatias/veterinária , Brasil/epidemiologia , Bovinos , Doenças dos Bovinos/epidemiologia , Feminino
8.
Medicine (Baltimore) ; 98(18): e15548, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31045846

RESUMO

RATIONALE: Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis. Petroclival RDD is extremely rare. To the best of our knowledge, only 7 cases of petroclival RDD have been reported so far. Herein, we present the 8th case of intracranial RDD with the petroclival and parasellar involvement mimicking multiple meningiomas. PATIENT CONCERNS: A 57-year-old woman presented with a 1-year history of vision diminution and 1-month hearing loss in her right ear. DIAGNOSES: Contrast-enhanced Magnetic resonance imaging (MRI) of the brain demonstrated multiple well-defined, homogenous mass which closely related to the dura mater in the bilateral parasellar and petroclival regions range from the basement of anterior to posterior cranial fossa. The lesions were T1 isointense, T2 hypointense, and homogeneously enhanced. Initial diagnosis of multiple meningiomas was made according to MRI findings. Final diagnosis of RDD was confirmed by histopathological and immunohistochemical examinations after subtotal surgical resection. INTERVENTIONS: The patient received subtotal resection because multiple lesions were extensive. OUTCOMES: The vision diminution recovered well after the surgery but the hearing loss in her right ear was still persisted. LESSONS: Although rare, a standard RDD typically are dural-based, extra-axial, well-circumscribed masses mimicking meningioma, and presenting with characterized hypo to isointense on T1-weighted images, hypo to isointense on T2-weighted images, and obvious enhancement. Resection of the intracranial lesion is the most effective treatment. In case of subtotal resection, the application of adjunctive radiotherapy and/or steroid agents should be advised. Final diagnosis of RDD should be confirmed by histopathological and immunohistochemical examinations.


Assuntos
Encefalopatias/diagnóstico , Histiocitose Sinusal/diagnóstico , Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Encefalopatias/patologia , Diagnóstico Diferencial , Feminino , Histiocitose Sinusal/patologia , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Base do Crânio/diagnóstico por imagem , Base do Crânio/patologia
9.
Hum Genet ; 138(7): 749-756, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31079202

RESUMO

Cytochrome c oxidase 20 (COX20)/FAM36A encodes a conserved protein that is important for the assembly of COX, complex IV of the mitochondrial respiratory chain. A homozygous mutation (p.Thr52Pro) in COX20 gene has been previously described to cause muscle hypotonia and ataxia. In this study, we describe two patients from a non-consanguineous family exhibiting autosomal recessive sensory-dominant axonal neuropathy and static encephalopathy. The whole-exome sequencing analysis revealed that both patients harbored compound heterozygous mutations (p.Lys14Arg and p.Trp74Cys) of COX20 gene. The pathogenicity of the variants was further supported by morphological alternations of mitochondria observed in sural nerve and decreased COX20 protein level of peripheral blood leucocytes derived from the patients. In conclusion, COX20 might be considered as a candidate gene for the complex inherited disease. This observation broadens the clinical and genetic spectrum of COX20-related disease. However, due to the limitation of a single-family study, additional cases and studies are definitely needed to further confirm the association.


Assuntos
Encefalopatias/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Deformidades do Pé/genética , Neuropatia Axonal Gigante/genética , Mutação , Adolescente , Adulto , Encefalopatias/patologia , Feminino , Deformidades do Pé/patologia , Neuropatia Axonal Gigante/patologia , Humanos , Masculino , Adulto Jovem
10.
PLoS Pathog ; 15(4): e1007712, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30970042

RESUMO

Although considerable evidence supports that misfolded prion protein (PrPSc) is the principal component of "prions", underpinning both transmissibility and neurotoxicity, clear consensus around a number of fundamental aspects of pathogenesis has not been achieved, including the time of appearance of neurotoxic species during disease evolution. Utilizing a recently reported electrophysiology paradigm, we assessed the acute synaptotoxicity of ex vivo PrPSc prepared as crude homogenates from brains of M1000 infected wild-type mice (cM1000) harvested at time-points representing 30%, 50%, 70% and 100% of the terminal stage of disease (TSD). Acute synaptotoxicity was assessed by measuring the capacity of cM1000 to impair hippocampal CA1 region long-term potentiation (LTP) and post-tetanic potentiation (PTP) in explant slices. Of particular note, cM1000 from 30% of the TSD was able to cause significant impairment of LTP and PTP, with the induced failure of LTP increasing over subsequent time-points while the capacity of cM1000 to induce PTP failure appeared maximal even at this early stage of disease progression. Evidence that the synaptotoxicity directly related to PrP species was demonstrated by the significant rescue of LTP dysfunction at each time-point through immuno-depletion of >50% of total PrP species from cM1000 preparations. Moreover, similar to our previous observations at the terminal stage of M1000 prion disease, size fractionation chromatography revealed that capacity for acute synpatotoxicity correlated with predominance of oligomeric PrP species in infected brains across all time points, with the profile appearing maximised by 50% of the TSD. Using enhanced sensitivity western blotting, modestly proteinase K (PK)-resistant PrPSc was detectable at very low levels in cM1000 at 30% of the TSD, becoming robustly detectable by 70% of the TSD at which time substantial levels of highly PK-resistant PrPSc was also evident. Further illustrating the biochemical evolution of acutely synaptotoxic species the synaptotoxicity of cM1000 from 30%, 50% and 70% of the TSD, but not at 100% TSD, was abolished by digestion of immuno-captured PrP species with mild PK treatment (5µg/ml for an hour at 37°C), demonstrating that the predominant synaptotoxic PrPSc species up to and including 70% of the TSD were proteinase-sensitive. Overall, these findings in combination with our previous assessments of transmitting prions support that synaptotoxic and infectious M1000 PrPSc species co-exist from at least 30% of the TSD, simultaneously increasing thereafter, albeit with eventual plateauing of transmitting conformers.


Assuntos
Evolução Biológica , Encefalopatias/patologia , Proteínas PrPSc/metabolismo , Doenças Priônicas/patologia , Príons/patogenicidade , Sinapses/patologia , Animais , Encefalopatias/etiologia , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Doenças Priônicas/etiologia , Proteólise , Sinapses/metabolismo
11.
Int J Mol Sci ; 20(8)2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31018603

RESUMO

Dual-specificity protein phosphatases comprise a protein phosphatase subfamily with selectivity towards mitogen-activated protein (MAP) kinases, also named MKPs, or mitogen-activated protein kinase (MAPK) phosphatases. As powerful regulators of the intensity and duration of MAPK signaling, a relevant role is envisioned for dual-specificity protein phosphatases (DUSPs) in the regulation of biological processes in the nervous system, such as differentiation, synaptic plasticity, and survival. Important neural mediators include nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) that contribute to DUSP transcriptional induction and post-translational mechanisms of DUSP protein stabilization to maintain neuronal survival and differentiation. Potent DUSP gene inducers also include cannabinoids, which preserve DUSP activity in inflammatory conditions. Additionally, nucleotides activating P2X7 and P2Y13 nucleotide receptors behave as novel players in the regulation of DUSP function. They increase cell survival in stressful conditions, regulating DUSP protein turnover and inducing DUSP gene expression. In general terms, in the context of neural cells exposed to damaging conditions, the recovery of DUSP activity is neuroprotective and counteracts pro-apoptotic over-activation of p38 and JNK. In addition, remarkable changes in DUSP function take place during the onset of neuropathologies. The restoration of proper DUSP levels and recovery of MAPK homeostasis underlie the therapeutic effect, indicating that DUSPs can be relevant targets for brain diseases.


Assuntos
Fosfatases de Especificidade Dupla/metabolismo , Neuroglia/metabolismo , Neurônios/metabolismo , Animais , Encefalopatias/metabolismo , Encefalopatias/patologia , Humanos , Inflamação/metabolismo , Inflamação/patologia , Fatores de Crescimento Neural/metabolismo , Neurogênese , Neuroglia/citologia , Neuroglia/patologia , Neurônios/citologia , Neurônios/patologia , Estresse Oxidativo , Dor/metabolismo , Dor/patologia
12.
EBioMedicine ; 43: 447-453, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31003928

RESUMO

BACKGROUND: Recent deep learning models have shown remarkable accuracy for the diagnostic classification. However, they have limitations in clinical application due to the gap between the training cohorts and real-world data. We aimed to develop a model trained only by normal brain PET data with an unsupervised manner to identify an abnormality in various disorders as imaging data of the clinical routine. METHODS: Using variational autoencoder, a type of unsupervised learning, Abnormality Score was defined as how far a given brain image is from the normal data. The model was applied to FDG PET data of Alzheimer's disease (AD) and mild cognitive impairment (MCI) and clinical routine FDG PET data for assessing behavioral abnormality and seizures. Accuracy was measured by the area under curve (AUC) of receiver-operating-characteristic (ROC) curve. We investigated whether deep learning has additional benefits with experts' visual interpretation to identify abnormal patterns. FINDINGS: The AUC of the ROC curve for differentiating AD was 0.90. The changes in cognitive scores from baseline to 2-year follow-up were significantly correlated with Abnormality Score at baseline. The AUC of the ROC curve for discriminating patients with various disorders from controls was 0.74. Experts' visual interpretation was helped by the deep learning model to identify abnormal patterns in 60% of cases initially not identified without the model. INTERPRETATION: We suggest that deep learning model trained only by normal data was applicable for identifying wide-range of abnormalities in brain diseases, even uncommon ones, proposing its possible use for interpreting real-world clinical data.


Assuntos
Encefalopatias/diagnóstico por imagem , Encefalopatias/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Aprendizado Profundo , Tomografia por Emissão de Pósitrons , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Área Sob a Curva , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Fluordesoxiglucose F18 , Humanos , Processamento de Imagem Assistida por Computador , Neuroimagem , Tomografia por Emissão de Pósitrons/métodos , Curva ROC
13.
BMC Neurol ; 19(1): 59, 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30971206

RESUMO

BACKGROUND: Scattered extracellular deposits of amyloid within the brain parenchyma can be found in a heterogeneous group of diseases. Its condensed accumulation in the white matter without evidence for systemic amyloidosis is known as primary brain amyloidoma (PBA). Although originally considered as a tumor-like lesion by its space-occupying effect, this condition displays also common hallmarks of a neurodegenerative disorder. CASE PRESENTATION: A 50-year-old woman presented with a mild cognitive decline and seizures with a right temporal, irregular and contrast-enhancing mass on magnetic resonance imaging. Suspecting a high-grade glioma, the firm tumor was subtotally resected. Neuropathological examination showed no glioma, but distinct features of a neurodegenerative disorder. The lesion was composed of amyloid AL λ aggregating within the brain parenchyma as well as the adjacent vessels, partially obstructing the vascular lumina. Immunostaining confirmed a distinct perivascular inflammatory reaction. After removal of the PBA, mnestic impairments improved considerably, the clinical course and MRI-results are stable in the 8-year follow-up. CONCLUSION: Based on our histopathological findings, we propose to regard the clinicopathological entity of PBA as an overlap between a neoplastic and neurodegenerative disorder. Since the lesions are locally restricted, they might be amenable to surgery with the prospect of a definite cure.


Assuntos
Amiloidose/patologia , Encefalopatias/patologia , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/patologia , Feminino , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade
14.
BMC Neurol ; 19(1): 60, 2019 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-30979360

RESUMO

BACKGROUND: Primary familial brain calcification is a rare autosomal dominant or recessive neurodegenerative disease, characterized by bilateral brain calcifications in different areas of the brain. It is a clinically heterogeneous disease and patients are reported to exhibit a wide spectrum of neurological and psychiatric symptoms. Mutations in five genes have been identified so far including SLC20A2, PDGFRB, PDGFB, XPR1, and MYORG. PDGFRB encodes the platelet-derived growth factor receptor-beta, and is expressed in neurons, vascular smooth muscle cells and pericytes. Patients with a PDGFRB mutation seem to exhibit a milder phenotype and milder brain calcification on brain imaging than patients with SLC20A2 and PDGFB mutations. However, this is based on a few observations so far. CASE PRESENTATION: We present a Danish family with bilateral brain calcifications and mild clinical symptoms of primary familial brain calcification, segregating with a novel PDGFRB sequence variant: c.1834G > A; p.(Gly612Arg), detected by whole exome sequencing. The variant results in physiochemical changes at the amino acid level, and affects a highly conserved nucleotide as well as amino acid. It is located in the tyrosine kinase domain of PDGFRß. Segregation analysis and in silico analyses predicted the missense variant to be disease causing. CONCLUSION: Our study confirms that PDGFRB mutation carriers in general have a mild clinical phenotype, and basal ganglia calcifications can be detected by a CT scan, also in asymptomatic mutation carriers.


Assuntos
Encefalopatias/genética , Calcinose/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Encefalopatias/patologia , Calcinose/patologia , Dinamarca , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/patologia , Linhagem , Tomografia Computadorizada por Raios X
15.
Int J Mol Sci ; 20(5)2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30818802

RESUMO

Astrocytes are the most abundant cell type in the CNS (central nervous system). They exert multiple functions during development and in the adult CNS that are essential for brain homeostasis. Both cation and anion channel activities have been identified in astrocytes and it is believed that they play key roles in astrocyte function. Whereas the proteins and the physiological roles assigned to cation channels are becoming very clear, the study of astrocytic chloride channels is in its early stages. In recent years, we have moved from the identification of chloride channel activities present in astrocyte primary culture to the identification of the proteins involved in these activities, the determination of their 3D structure and attempts to gain insights about their physiological role. Here, we review the recent findings related to the main chloride channels identified in astrocytes: the voltage-dependent ClC-2, the calcium-activated bestrophin, the volume-activated VRAC (volume-regulated anion channel) and the stress-activated Maxi-Cl-. We discuss key aspects of channel biophysics and structure with a focus on their role in glial physiology and human disease.


Assuntos
Astrócitos/metabolismo , Encefalopatias/metabolismo , Encefalopatias/patologia , Encéfalo/metabolismo , Encéfalo/patologia , Canais de Cloreto/química , Canais de Cloreto/metabolismo , Homeostase , Animais , Humanos , Modelos Biológicos
16.
Intern Med ; 58(13): 1947-1951, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30918173

RESUMO

A 64-year-old man previously diagnosed with Waldenstrom's macroglobulinemia presented to our hospital with confusion. Magnetic resonance imaging (MRI) revealed diffuse meningeal enhancement. The patient was diagnosed with Bing-Neel syndrome (BNS) based on an elevated IgM index and the presence of monoclonal IgM protein, as detected by immunofixation electrophoresis of the cerebrospinal fluid. The patient underwent intrathecal and systemic chemotherapy but ultimately died of pneumonia. An autopsy revealed extensive meningeal and perivascular infiltration by malignant cells throughout the brain and spine. Thus, BNS may cause more extensive malignant infiltration into the central nervous system than is revealed by MRI.


Assuntos
Encefalopatias/tratamento farmacológico , Encefalopatias/patologia , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/patologia , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/patologia , Autopsia , Encefalopatias/diagnóstico , Encefalopatias/mortalidade , Citarabina/uso terapêutico , Dexametasona/uso terapêutico , Evolução Fatal , Humanos , Imunossupressores/uso terapêutico , Imagem por Ressonância Magnética , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Doenças Neurodegenerativas/mortalidade , Radiografia , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/mortalidade
17.
Malar J ; 18(1): 74, 2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30871543

RESUMO

BACKGROUND: Previous studies have documented a spectrum of brain magnetic resonance imaging (MRI) abnormalities in patients with cerebral malaria, but little is known about the prevalence of such abnormalities in patients with non-cerebral malaria. The aim of this study was to assess the frequency of brain MRI findings in returning travellers with non-cerebral malaria. METHODS: A total of 17 inpatients with microscopically confirmed Plasmodium falciparum non-cerebral malaria underwent structural brain MRI at 3.0 Tesla, including susceptibility-weighted imaging (SWI). Presence of imaging findings was recorded and correlated with clinical findings and parasitaemia. RESULTS: Structural brain abnormalities included a hyperintense lesion of the splenium on T2-weighted imaging (n = 3) accompanied by visible diffusion restriction (n = 2). Isolated brain microhaemorrhage was detected in 3 patients. T2-hyperintense signal abnormalities of the white matter ranged from absent to diffuse (n = 10 had 0-5 lesions, n = 5 had 5-20 lesions and 2 patients had more than 50 lesions). Imaging findings were not associated with parasitaemia or HRP2 levels. CONCLUSION: Brain MRI reveals a considerable frequency of T2-hyperintense splenial lesions in returning travellers with non-cerebral malaria, which appears to be independent of parasitaemia.


Assuntos
Encefalopatias/diagnóstico por imagem , Encefalopatias/patologia , Doenças Transmissíveis Importadas/patologia , Imagem por Ressonância Magnética , Malária Falciparum/patologia , Adulto , Encefalopatias/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
18.
Neurol Sci ; 40(Suppl 1): 49-54, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30906964

RESUMO

In the last 20 years, we observed significant improvements in the use of magnetic resonance imaging (MRI) for the evaluation of patients affected by migraine. Before these technological advances, knowledge of the pathogenesis of migraine was particularly based on clinical assessment. Complementary to clinical evaluation, conventional MRI provides both specific information for differential diagnosis (particularly if cortical or subcortical lesions are detected in the migrainous brain) and unsurpassable opportunities in migraine research. However, the correlations between brain structural and functional alterations and both the clinical manifestation of the disease and the individual history of the patient remains uncertain. Both quantitative and functional MR-based techniques have a great potential to better provide insights into human brain structures and possible links between brain areas and complex brain networks that could be involved in the pathophysiology of migraine. Morphometric and functional MRI approaches are contributing to better elucidate the mechanisms that underlie the pain mechanisms and functional adaptation in migraine patients. All these information support the view of migraine as a complex brain disorder involving different cortical and subcortical areas.


Assuntos
Encefalopatias/fisiopatologia , Encéfalo/patologia , Imagem por Ressonância Magnética , Transtornos de Enxaqueca/fisiopatologia , Encéfalo/fisiopatologia , Encefalopatias/patologia , Diagnóstico Diferencial , Humanos , Imagem por Ressonância Magnética/métodos , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/patologia , Rede Nervosa/patologia , Rede Nervosa/fisiopatologia
19.
Rinsho Shinkeigaku ; 59(2): 93-97, 2019 Feb 23.
Artigo em Japonês | MEDLINE | ID: mdl-30700686

RESUMO

We herein report a 67-year-old female who presented with progressive dementia and disturbance of consciousness. Brain CT showed multiple subcortical calcifications with edema. Enhanced CT showed multiple abnormal vessels in the left hemisphere. Electroencephalography indicated diffuse spike and slow wave complex, so non-convulsive status epilepticus was diagnosed. Cerebral angiography revealed several feeder arteries with retrograde leptomeningeal venous drainage. We diagnosed her with Borden type III cerebral dural arteriovenous fistulas. Trans-arterial embolization with n-butyl-2-cyanoacrylate was performed, and she has experienced no epileptic attacks for at least ten months. Calcification changes are sometimes seen in Borden type II dural arteriovenous fistulas but not in aggressive types, such as Borden type III. It is important to suspect dural arteriovenous fistulas when we encounter patients with progressive dementia or/and epilepsy with cerebral calcification lesions, as this may be a treatable disease condition.


Assuntos
Encefalopatias/diagnóstico por imagem , Encefalopatias/patologia , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Calcinose/diagnóstico por imagem , Calcinose/patologia , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/patologia , Tomografia Computadorizada por Raios X , Idoso , Malformações Vasculares do Sistema Nervoso Central/classificação , Malformações Vasculares do Sistema Nervoso Central/cirurgia , Angiografia Cerebral , Demência , Progressão da Doença , Embolização Terapêutica , Embucrilato/administração & dosagem , Procedimentos Endovasculares , Feminino , Humanos , Estado Epiléptico
20.
Nat Commun ; 10(1): 708, 2019 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-30755616

RESUMO

Aminoacyl tRNA synthetases (ARSs) link specific amino acids with their cognate transfer RNAs in a critical early step of protein translation. Mutations in ARSs have emerged as a cause of recessive, often complex neurological disease traits. Here we report an allelic series consisting of seven novel and two previously reported biallelic variants in valyl-tRNA synthetase (VARS) in ten patients with a developmental encephalopathy with microcephaly, often associated with early-onset epilepsy. In silico, in vitro, and yeast complementation assays demonstrate that the underlying pathomechanism of these mutations is most likely a loss of protein function. Zebrafish modeling accurately recapitulated some of the key neurological disease traits. These results provide both genetic and biological insights into neurodevelopmental disease and pave the way for further in-depth research on ARS related recessive disorders and precision therapies.


Assuntos
Encefalopatias/genética , Microcefalia/genética , Valina-tRNA Ligase/genética , Alelos , Animais , Encefalopatias/enzimologia , Encefalopatias/patologia , Linhagem Celular , Modelos Animais de Doenças , Epilepsia/enzimologia , Epilepsia/genética , Epilepsia/patologia , Feminino , Fibroblastos , Técnicas de Inativação de Genes , Predisposição Genética para Doença , Humanos , Mutação com Perda de Função , Masculino , Microcefalia/enzimologia , Microcefalia/patologia , Modelos Moleculares , Transtornos do Neurodesenvolvimento/enzimologia , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/patologia , Linhagem , Prosencéfalo/patologia , Peixe-Zebra
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