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1.
Fortschr Neurol Psychiatr ; 87(10): 571-575, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31627239

RESUMO

The CLIPPERS syndrome is a chronic, inflammatory disorder of the central nervous system of unknown etiology, which was first described in 2010 by Pittock and colleagues. It is characterized by typical magnetic resonance imaging (MRI) changes with lesions mainly in the brainstem, a perivascular, lymphohistiocytic inflammatory process and significant improvement under glucocorticoid therapy. Here we describe the case of a 40-year-old male who presented initially with typical clinical and radiological signs of CLIPPERS syndrome and who achieved complete remission under immunosuppressive therapy. Two years later, he presented with severe headaches. The MRI showed a reappearance of the lesion in the cerebellum, but now with a confluent character. The first brain biopsy showed lymphoproliferation. A second brain biopsy could finally confirm the suspected diagnosis of a primary CNS lymphoma.


Assuntos
Tronco Encefálico/diagnóstico por imagem , Tronco Encefálico/patologia , Neoplasias do Sistema Nervoso Central/diagnóstico , Linfoma/diagnóstico , Adulto , Biópsia , Neoplasias do Sistema Nervoso Central/patologia , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Cefaleia , Humanos , Linfoma/patologia , Imagem por Ressonância Magnética , Masculino , Síndrome
2.
J Headache Pain ; 20(1): 93, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477012

RESUMO

BACKGROUND: Increasing evidence has suggested that the cerebellum is associated with pain and migraine. In addition, the descending pain system of the brainstem is the major site of trigeminal pain processing and modulation and has been discussed as a main player in the pathophysiology of migraine. Cerebellar and brainstem structural changes associated with migraineurs remain to be further investigated. METHODS: Voxel-based morphometry (VBM) (50 controls, 50 migraineurs without aura (MWoAs)) and diffusion tensor imaging (DTI) (46 controls, 46 MWoAs) were used to assess cerebellum and brainstem anatomical alterations associated with MWoAs. We utilized a spatially unbiased infratentorial template toolbox (SUIT) to perform cerebellum and brainstem optimized VBM and DTI analysis. We extracted the average diffusion values from a probabilistic cerebellar white matter atlas to investigate whether MWoAs exhibited microstructure alterations in the cerebellar peduncle tracts. RESULTS: MWoAs showed decreased fractional anisotropy (FA) in the vermis VI extending to the bilateral lobules V and VI of the cerebellum. We also found higher axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) in the right inferior cerebellum peduncle tract in MWoAs. MWoAs exhibited both reduced gray matter volume and increased AD, MD and RD in the spinal trigeminal nucleus (SpV). CONCLUSION: MWoAs exhibited microstructural changes in the cerebellum and the local brainstem. These structural differences might contribute to dysfunction of the transmission and modulation of noxious information, trigeminal nociception, and conduction and integration of multimodal information in MWoAs. These findings further suggest involvement of the cerebellum and the brainstem in the pathology of migraine without aura.


Assuntos
Tronco Encefálico/patologia , Cerebelo/patologia , Enxaqueca sem Aura/patologia , Anisotropia , Tronco Encefálico/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Imagem de Tensor de Difusão , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Humanos , Masculino , Enxaqueca sem Aura/diagnóstico por imagem , Núcleo Espinal do Trigêmeo/diagnóstico por imagem , Núcleo Espinal do Trigêmeo/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
3.
Postgrad Med ; 131(7): 533-538, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31478419

RESUMO

Introduction: Depression in patients with mild cognitive impairment (MCI) and dementia of the Alzheimer's type (AD) is associated with worse prognosis. Indeed, depressed MCI patients have worse cognitive performance and greater loss of gray-matter volume in several brain areas. To date, knowledge of the factors that can mitigate this detrimental effect is still limited. The aim of the present study was to understand in what way cognitive reserve/brain reserve and depression interact and are linked to regional atrophy in early stage AD. Methods: Depression was evaluated with the Patient Health Questionnaire-9 in 90 patients with early AD, and a cutoff of ≥ 5 was used to separate depressed (n = 44) from non-depressed (n = 46) patients. Each group was further stratified into high/low cognitive reserve/brain reserve. Cognitive reserve was calculated using years of education as proxy, while normalized parenchymal volumes were used to estimate brain reserve. Voxel-based morphometry was carried out to extract and analyze gray-matter maps. 2 × 2 ANCOVAs were run to test the effect of the reserve-by-depression interaction on gray matter. Age and hippocampal ratio were used as covariates. Composite indices of major cognitive domains were also analyzed with comparable models. Results: No reserve-by-depression interaction was found in the analytical models of gray matter. Depression was associated with less gray matter volume in the cerebellum and parahippocampal gyrus. The brain reserve-by-depression interaction was a significant predictor of executive functioning. Among those with high brain reserve, depressed patients had poorer executive skills. No significant results were found in association with cognitive reserve. Conclusion: These findings suggest that brain reserve may modulate the association between neurodegeneration and depression in patients with MCI and dementia of the AD type, influencing in particular executive functioning.


Assuntos
Doença de Alzheimer/psicologia , Disfunção Cognitiva/psicologia , Reserva Cognitiva , Depressão/psicologia , Substância Cinzenta/diagnóstico por imagem , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/fisiopatologia , Atrofia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/fisiopatologia , Depressão/diagnóstico por imagem , Depressão/fisiopatologia , Feminino , Substância Cinzenta/patologia , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Giro Para-Hipocampal/diagnóstico por imagem , Giro Para-Hipocampal/patologia , Questionário de Saúde do Paciente
4.
Medicine (Baltimore) ; 98(35): e16841, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464910

RESUMO

RATIONALE: Multiple primary central nervous system lymphoma (MPCNSL) is a rare disease with differential diagnosis and treatment. As the underlying pathogenesis is not yet clarified, the early-stage clinical manifestations are occult and atypical. Also, the imaging manifestations are not specific, which is challenging for the clinical diagnosis and treatment. Therefore, additional clinical research is essential to understand the etiology of the disease. PATIENT CONCERNS: A 63-year-old male patient suffered from MPCNSLs but without typical clinical manifestations. The findings of the imaging examination were as follows. Magnetic resonance imaging (MRI) showed long T1 and T2 signal shadows in the right frontal lobe, right hippocampus, right cerebellar hemisphere, and the left occipital lobe. In addition, patchy T1-enhanced signal shadows were observed in the right frontal lobe and around the midline. Frontal lesions were detected in the magnetic resonance spectroscopy (MRS), Cho peak increased, and N-acetylaspartate (NAA) peak decreased. On the other hand, in the diffusion weighted imaging (DWI), apparent dispersion coefficient (ADC) showed low-value changes and high signal changes. The positron emission tomography-computed tomography (PET-CT) displayed radioactive accumulation in the right frontal lobe. DIAGNOSIS: Multiple primary central nervous system lymphoma. INTERVENTIONS: The patient received some conservative medical treatment, but his condition continued to worsen. Finally, he received a pathological biopsy, and refused further treatment after the result was reported. OUTCOMES: The patient died 1 week after biopsy, and the course of disease was about 100 days. LESSONS: PCNSL is a primary intracranial malignancy with low incidence and a high degree of malignancy and specificity in clinical manifestations. To facilitate early clinical treatment and improve the long-term survival of patients, it is necessary to master the imaging diagnostic methods and its features. The comprehensive application of multiple imaging examinations, such as CT, MRI, PET/CT, and PET/MRI, as well as, cerebrospinal fluid cytology can greatly improve the diagnosis of PCNSL.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Linfoma não Hodgkin/diagnóstico por imagem , Imagem Multimodal/métodos , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Imagem de Difusão por Ressonância Magnética , Evolução Fatal , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/patologia , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/patologia , Lobo Occipital/diagnóstico por imagem , Lobo Occipital/patologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
5.
Nature ; 572(7767): 74-79, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31341285

RESUMO

Medulloblastoma is a malignant childhood cerebellar tumour type that comprises distinct molecular subgroups. Whereas genomic characteristics of these subgroups are well defined, the extent to which cellular diversity underlies their divergent biology and clinical behaviour remains largely unexplored. Here we used single-cell transcriptomics to investigate intra- and intertumoral heterogeneity in 25 medulloblastomas spanning all molecular subgroups. WNT, SHH and Group 3 tumours comprised subgroup-specific undifferentiated and differentiated neuronal-like malignant populations, whereas Group 4 tumours consisted exclusively of differentiated neuronal-like neoplastic cells. SHH tumours closely resembled granule neurons of varying differentiation states that correlated with patient age. Group 3 and Group 4 tumours exhibited a developmental trajectory from primitive progenitor-like to more mature neuronal-like cells, the relative proportions of which distinguished these subgroups. Cross-species transcriptomics defined distinct glutamatergic populations as putative cells-of-origin for SHH and Group 4 subtypes. Collectively, these data provide insights into the cellular and developmental states underlying subtype-specific medulloblastoma biology.


Assuntos
Genômica , Meduloblastoma/genética , Meduloblastoma/patologia , Análise de Célula Única , Transcriptoma , Adolescente , Adulto , Animais , Linhagem da Célula , Cerebelo/metabolismo , Cerebelo/patologia , Criança , Pré-Escolar , Variações do Número de Cópias de DNA , Regulação Neoplásica da Expressão Gênica , Ácido Glutâmico/metabolismo , Humanos , Lactente , Meduloblastoma/classificação , Camundongos , Neurônios/metabolismo , Neurônios/patologia
6.
BMC Neurol ; 19(1): 124, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31189472

RESUMO

BACKGROUND: Isolated posterior inferior cerebellar artery dissections can cause subarachnoid hemorrhages or infarctions. Surgical and endovascular treatments for hemorrhagic stroke cases and medical treatments using antithrombotic agents for ischemic stroke cases have been performed, but there are very few reports on nonstroke isolated posterior inferior cerebellar artery dissections, and the treatment strategy for nonstroke cases has not been established. CASE PRESENTATION: A 48-year-old healthy male felt a severe, throbbing headache on the right side and came to our clinic on the fourth day following onset. MRI examinations revealed a right posterior inferior cerebellar artery dissection and showed no infarctions or hemorrhages. He was observed carefully with continuous monitoring of blood pressure, hydrated sufficiently, and given analgesic anti-inflammatory agents. Two weeks later, the dissected vessel's diameter grew to the maximum size, though the patient's headache rapidly improved around that day. Surgical or endovascular treatments for prevention of subarachnoid hemorrhage were recommended, but careful conservative therapy was continued in accordance with the patient's wishes. Gradually, the dissection finding improved. Four months later, MRI examinations showed his right posterior inferior cerebellar artery was almost normal in size and shape. CONCLUSIONS: This is the first detailed report on a nonstroke isolated posterior inferior cerebellar artery dissection that spontaneously occurred and healed, observed by serial high-resolution MRI examinations.


Assuntos
Aneurisma Dissecante/patologia , Aneurisma Intracraniano/patologia , Remissão Espontânea , Cerebelo/irrigação sanguínea , Cerebelo/patologia , Cefaleia/etiologia , Humanos , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
7.
Eur J Paediatr Neurol ; 23(4): 604-608, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31147107

RESUMO

Pediatric abusive head trauma (AHT) or non accidental head trauma (NAHT) is a major cause of death from trauma in children under 2 years of age. Main etiological factor for non accidental head trauma is shaking a baby, causing brain injury by rotational head acceleration and deceleration. The consequent brain damage as shown by magnetic resonance imaging (MRI) is subdural haemorrhage and to a lesser extent parenchymal injuries of variable severity. Involvement of the cerebellum has very rarely been described. We report the clinical history and the development of cerebral magnetic resonance imaging findings in two children with serious brain injury following probable shaking who presented the typical "triad" with subdural haematoma, retinal haemorrhage and encephalopathy. We want to draw attention to cerebellar involvement characterized by cortico-subcortical signal alterations most prominent on T2w images following diffusion changes during the acute period. We discuss cerebellar involvement as a sign of higher severity of AHT which is probably underrecognized.


Assuntos
Lesões Encefálicas/patologia , Cerebelo/lesões , Cerebelo/patologia , Maus-Tratos Infantis , Traumatismos Craniocerebrais/patologia , Lesões Encefálicas/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Maus-Tratos Infantis/diagnóstico , Traumatismos Craniocerebrais/diagnóstico por imagem , Feminino , Humanos , Lactente , Imagem por Ressonância Magnética/métodos , Masculino
8.
Life Sci ; 229: 180-186, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31077720

RESUMO

AIMS: The present study aimed to verify changes in cerebellar and plasmatic expression of miRNAs after the chronic consumption of ethanol and caffeine in the UChB rat, an experimental model for alcoholism. MATERIAL AND METHODS: Male rats at 5 months of age, were divided into the following groups (n = 10/group): 1. Ethanol (UChB rats receiving 10% ethanol solution and water ad libitum); 2. Ethanol + caffeine (UChB rats receiving 10% ethanol solution + 3g/l caffeine and water ad libitum); 3. Control (rats receiving water ad libitum). The cerebellum and plasma of the animals were collected and processed by RT-PCR for the miRNAs-155-5p, -146a-5p, -126-3p, -132-3p, -339-5p. KEY FINDINGS: Ethanol and caffeine were capable of regulating the expression of miRNAs associated with the inflammatory process in the tissue and plasma of the UChB rats. Increased expression of the analyzed miRNAs-155-5p, -146a-5p, -126-3p, -132-3p was observed for the cerebellar tissue in the Ethanol group and reduced expression of them in the Ethanol + caffeine group. In plasma, caffeine significantly elevated the miR-126-3p and miR-132-3p levels and decreased miR-155-5p levels. Ethanol consumption increased miR-146a-5p expression and decreased miR-339-5p levels. In brief, altered plasmatic levels of the miRNAs did not reflect the miRNAs levels found in cerebellar tissue. SIGNIFICANCE: Considering the results herein, we concluded that ethanol predisposes to an inflammatory process while caffeine has a neuroprotective effect on the cerebellar tissue.


Assuntos
Cafeína/farmacologia , Cerebelo/patologia , Etanol/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , MicroRNAs/genética , Plasma/metabolismo , Animais , Cafeína/administração & dosagem , Depressores do Sistema Nervoso Central/administração & dosagem , Depressores do Sistema Nervoso Central/farmacologia , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/farmacologia , Cerebelo/efeitos dos fármacos , Cerebelo/metabolismo , Etanol/administração & dosagem , Perfilação da Expressão Gênica , Masculino , Ratos
9.
Neuropsychology ; 33(5): 725-738, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31094552

RESUMO

BACKGROUND: Idiopathic descent of cerebellar tonsils into the cervical spine in Chiari malformation Type I (CMI) is typically associated with occipital headache. Accumulating evidence from experimental studies suggests cognitive effects of CMI. The aim of the current study was to examine the relationship between cognition and CMI using a battery of standardized neuropsychological and symptom inventory instruments. METHOD: Eighteen untreated adults with CMI, and 18 gender, age, and education matched healthy controls completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and standardized measures of pain, mood, and disability. Morphometric measurements of key neural and osseous elements were also obtained from structural brain magnetic resonance images, for correlation with symptom outcomes. RESULTS: CMI patients exhibited deficits in RBANS attention, immediate memory, delayed memory, and total score. After controlling for pain and associated affective disturbance, the significant group effect for RBANS attention remained. CMI patients also presented seven morphometric differences comprising the cerebellum and posterior cranial fossa compartment that differed from healthy controls, some of which were associated with self-reported pain and disability. Notably, group differences in tonsillar position were associated with self-reported pain, disability, and delayed memory. CONCLUSION: Adult CMI is associated with domain-specific cognitive change, detectable using a standard clinical instrument. The extent of cognitive impairment is independent of pain or affective symptomatology and may be related to the key pathognomonic feature of the condition. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Malformação de Arnold-Chiari/complicações , Malformação de Arnold-Chiari/patologia , Cerebelo/patologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Fossa Craniana Posterior/patologia , Adolescente , Adulto , Cerebelo/diagnóstico por imagem , Fossa Craniana Posterior/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Adulto Jovem
10.
Mol Genet Metab ; 127(1): 107-115, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31101435

RESUMO

The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders characterized by progressive declines in neurological functions following normal development. The NCLs are distinguished from similar disorders by the accumulation of autofluorescent lysosomal storage bodies in neurons and many other cell types, and are classified as lysosomal storage diseases. At least 13 genes contain pathogenic sequence variants that underlie different forms of NCL. Naturally occurring canine NCLs can serve as models to develop better understanding of the disease pathologies and for preclinical evaluation of therapeutic interventions for these disorders. To date 14 sequence variants in 8 canine orthologs of human NCL genes have been found to cause progressive neurological disorders similar to human NCLs in 12 different dog breeds. A mixed breed dog with parents of uncertain breed background developed progressive neurological signs consistent with NCL starting at approximately 11 to 12 months of age, and when evaluated with magnetic resonance imaging at 21 months of age exhibited diffuse brain atrophy. Due to the severity of neurological decline the dog was euthanized at 23 months of age. Cerebellar and cerebral cortical neurons contained massive accumulations of autofluorescent storage bodies the contents of which had the appearance of tightly packed membranes. A whole genome sequence, generated with DNA from the affected dog contained a homozygous C-to-T transition at position 30,574,637 on chromosome 22 which is reflected in the mature CLN5 transcript (CLN5: c.619C > T) and converts a glutamine codon to a termination codon (p.Gln207Ter). The identical nonsense mutation has been previously associated with NCL in Border Collies, Australian Cattle Dogs, and a German Shepherd-Australian Cattle Dog mix. The current whole genome sequence and a previously generated whole genome sequence for an Australian Cattle Dog with NCL share a rare homozygous haplotype that extends for 87 kb surrounding 22: 30, 574, 637 and includes 21 polymorphic sites. When genotyped at 7 of these polymorphic sites, DNA samples from the German Shepherd-Australian Cattle Dog mix and from 5 Border Collies with NCL that were homozygous for the CLN5: c.619 T allele also shared this homozygous haplotype, suggesting that the NCL in all of these dogs stems from the same founding mutation event that may have predated the establishment of the modern dog breeds. If so, the CLN5 nonsence allele is probably segregating in other, as yet unidentified, breeds. Thus, dogs exhibiting similar NCL-like signs should be screened for this CLN5 nonsense allele regardless of breed.


Assuntos
Códon sem Sentido , Doenças do Cão/genética , Proteínas de Membrana/genética , Lipofuscinoses Ceroides Neuronais/veterinária , Animais , Austrália , Cruzamento , Cerebelo/patologia , Cães/genética , Homozigoto , Imagem por Ressonância Magnética , Lipofuscinoses Ceroides Neuronais/diagnóstico por imagem , Lipofuscinoses Ceroides Neuronais/genética , Linhagem , Sequenciamento Completo do Genoma
11.
N Engl J Med ; 380(15): 1433-1441, 2019 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-30970188

RESUMO

We report an inborn error of metabolism caused by an expansion of a GCA-repeat tract in the 5' untranslated region of the gene encoding glutaminase (GLS) that was identified through detailed clinical and biochemical phenotyping, combined with whole-genome sequencing. The expansion was observed in three unrelated patients who presented with an early-onset delay in overall development, progressive ataxia, and elevated levels of glutamine. In addition to ataxia, one patient also showed cerebellar atrophy. The expansion was associated with a relative deficiency of GLS messenger RNA transcribed from the expanded allele, which probably resulted from repeat-mediated chromatin changes upstream of the GLS repeat. Our discovery underscores the importance of careful examination of regions of the genome that are typically excluded from or poorly captured by exome sequencing.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/genética , Ataxia/genética , Deficiências do Desenvolvimento/genética , Glutaminase/deficiência , Glutaminase/genética , Glutamina/metabolismo , Repetições de Microssatélites , Mutação , Atrofia/genética , Cerebelo/patologia , Pré-Escolar , Feminino , Genótipo , Glutamina/análise , Humanos , Masculino , Fenótipo , Reação em Cadeia da Polimerase , Sequenciamento Completo do Genoma
12.
Cell Prolif ; 52(3): e12608, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30932251

RESUMO

OBJECTIVES: We performed histological, cellular and behavioural analyses of the effects of cyclophosphamide (CTX), a chemotherapeutic drug, in the developing cerebellum and aimed to provide valuable insights into clinical application of CTX in children. MATERIALS AND METHODS: C57BL/6 mice and Math1-dependent GFP expression transgenic mice were used in the research. H&E staining was performed to analyse histological effects of CTX in the cerebellum. Staining for EdU and TUNEL was used to estimate the cell proliferation and apoptosis. Rotarod test and hanging wire test were used to evaluate the behavioural functions. Immunofluorescent staining was used to identify the cell types. The differentiation markers and genes related to Sonic Hedgehog (SHH) signalling were measured via quantitative real-time PCR or immunoblotting. RESULTS: We found that while CTX induced a significant reduction in cell proliferation and increased apoptosis in the EGL in 48 hours, the behavioural functions and the multilayer laminar structure of cerebella were largely restored when the mice grew to adults. Mechanistically, granule neuron progenitors, driven by the SHH signalling, enhanced the capability of proliferation quickly after CTX administration was stopped, which allowed the developing cerebellum to catch up and to gradually replenish the injury. CONCLUSION: The chemotherapeutic agent CTX induces an immediate damage to the developing cerebellum, but the cerebellar multilayer laminar structure and motor function can be largely restored if the agent is stopped shortly after use.


Assuntos
Antineoplásicos Alquilantes/efeitos adversos , Comportamento Animal/efeitos dos fármacos , Cerebelo/efeitos dos fármacos , Ciclofosfamida/efeitos adversos , Animais , Animais Recém-Nascidos , Antineoplásicos Alquilantes/administração & dosagem , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cerebelo/crescimento & desenvolvimento , Cerebelo/patologia , Criança , Ciclofosfamida/administração & dosagem , Proteínas Hedgehog/metabolismo , Humanos , Injeções Intraperitoneais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Modelos Animais , Neurogênese/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
13.
Acta Neurol Scand ; 139(6): 491-496, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30977113

RESUMO

Essential tremor is a chronic neurological syndrome of heterogenous clinical phenotypes and multiple etiologies. Numerous studies have been done in order to investigate the pathological, neuroimaging, physiological, and clinical features of essential tremor; however, a clear pathophysiological mechanism has not been identified. One of the brain structures has been extensively investigated at the macroscopic and the microscopic level in the cerebellum. In the present study, we aim to discuss the main neuroimaging and neuropathological changes of the cerebellum in essential tremor.


Assuntos
Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Tremor Essencial/diagnóstico por imagem , Tremor Essencial/patologia , Humanos , Neuroimagem/métodos
14.
Neuron ; 102(1): 17-20, 2019 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-30946819

RESUMO

Recent research has identified a single factor accounting for broad risk to experience common forms of psychopathology. Structural alterations of cerebellar circuitry have emerged as a neural nexus of this broad risk, highlighting the cerebellum's importance for executive control.


Assuntos
Cerebelo/diagnóstico por imagem , Transtornos Mentais , Anisotropia , Cerebelo/patologia , Cerebelo/fisiopatologia , Suscetibilidade a Doenças , Neuroimagem Funcional , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Humanos , Imagem por Ressonância Magnética , Vias Neurais , Tamanho do Órgão , Ponte/diagnóstico por imagem , Ponte/patologia , Córtex Pré-Frontal/diagnóstico por imagem , Psicopatologia , Risco , Tálamo , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
15.
J Vet Med Sci ; 81(5): 747-749, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-30867352

RESUMO

A 9-year-old castrated male cat presented with sudden onset of paralysis in four limbs. Magnetic resonance imaging revealed an intramedullary lesion at C3, and lesions in the vermis and right hemisphere of the cerebellum, which were hyperintense on T2-weighted imaging. The cat was euthanized, and postmortem examination was performed. Grossly, transverse sectioning of the spinal cord revealed areas of malacia within the gray matter extending from C2 to C3. Histologically, the ventral spinal artery, the spinal intramedullary arteries and the arterioles of arachnoid in the cerebellum contained fibrocartilaginous emboli confirmed by metachromatic staining with toluidine blue. To our knowledge, this is the first report of fibrocartilaginous embolism involving both the cerebellum and cervical spinal cord in a cat.


Assuntos
Doenças das Cartilagens/veterinária , Doenças do Gato/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Embolia/veterinária , Medula Espinal/diagnóstico por imagem , Animais , Doenças das Cartilagens/diagnóstico por imagem , Doenças das Cartilagens/patologia , Doenças do Gato/patologia , Gatos , Cerebelo/patologia , Embolia/diagnóstico por imagem , Embolia/patologia , Imagem por Ressonância Magnética/veterinária , Masculino , Paralisia/etiologia , Paralisia/veterinária , Medula Espinal/patologia
16.
Food Chem Toxicol ; 127: 206-217, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30914353

RESUMO

The therapeutic effect of the hot water infusion of Cola nitida against hyperglycemia-induced neurotoxicity, cerebellar neurodegeneration and elemental deregulations was investigated in fructose-streptozotocin induced rat model of type 2 diabetes (T2D). A diabetic group was administered drinking water, two other diabetic groups were treated with C. nitida at 150 and 300 mg/kg bodyweight respectively, while another group was administered metformin (200 mg/kg bodyweight). Two other groups consisting of normal rats, were administered drinking water and C. nitida (300 mg/kg bodyweight). After 6 weeks of treatment, their brains were collected. Treatment with C. nitida led to suppression of oxidative stress, significantly elevating reduced glutathione (GSH) levels, superoxide dismutase and catalase activities, concomitant with depletion of malondialdehyde (MDA) levels. Acetylcholinesterase and ATPase activities were significantly inhibited in C. nitida-treated diabetic rats. Histological and microscopic analysis also revealed a restorative effect of C. nitida on T2D-altered distribution of elements, neurons and axonal nodes. Treatment with C. nitida also led to significant inhibition of Nrf2 expression in the cerebellar cortex. These results suggest the therapeutic effects of C. nitida in maintenance of the neuronal integrity and antioxidant status of the brain in T2D. These neuroprotective activities can be attributed to the identified alkaloid, caffeine in the infusion.


Assuntos
Lesões Encefálicas/tratamento farmacológico , Cerebelo/efeitos dos fármacos , Cola/química , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Hiperglicemia/complicações , Fator 2 Relacionado a NF-E2/metabolismo , Neurônios/patologia , Estresse Oxidativo , Extratos Vegetais/uso terapêutico , Regulação para Cima , Animais , Antioxidantes/farmacologia , Lesões Encefálicas/etiologia , Cerebelo/metabolismo , Cerebelo/patologia , Masculino , Oxirredução , Extratos Vegetais/farmacologia , Ratos Sprague-Dawley
17.
Oxid Med Cell Longev ; 2019: 6802424, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30911348

RESUMO

Ethanol (EtOH) binge drinking is characterized by high EtOH intake during few hours followed by withdrawal. Protection strategies against the damages generated by this binge are poorly explored. Thus, this study is aimed at investigating the protective role of treadmill physical exercise (PE) on the damage caused after repeated cycles of binge-like EtOH exposure in the oxidative biochemistry, morphology, and cerebellar function of rats from adolescence to adulthood. For this, animals were divided into four groups: control group (sedentary animals with doses of distilled water), exercised group (exercised animals with doses of distilled water), EtOH group (sedentary animals with doses of 3 g/kg/day of EtOH, 20% w/v), and exercised+EtOH group (exercised animals with previous mentioned doses of EtOH). The PE occurred on a running treadmill for 5 days a week for 4 weeks, and all doses of EtOH were administered through intragastric gavage in four repeated cycles of EtOH in a binge-like manner. After the EtOH protocol and PE, animals were submitted to open field and beam walking tests. In sequence, the cerebellums were collected for the biochemical and morphological analyses. Biochemical changes were analyzed by measurement of Trolox equivalent antioxidant capacity (TEAC), reduced glutathione content measurements (GSH), and measurement of nitrite and lipid peroxidation (LPO). In morphological analyses, Purkinje cell density evaluation and immunohistochemistry evaluation were measured by antimyelin basic protein (MBP) and antisynaptophysin (SYP). The present findings demonstrate that the binge drinking protocol induced oxidative biochemistry misbalance, from the decrease of TEAC levels and higher LPO related to tissue damage and motor impairment. In addition, we have shown for the first time that treadmill physical exercise reduced tissue and functional alterations displayed by EtOH exposure.


Assuntos
Envelhecimento/patologia , Bebedeira/patologia , Bebedeira/fisiopatologia , Cerebelo/patologia , Cerebelo/fisiopatologia , Etanol/efeitos adversos , Estresse Oxidativo , Condicionamento Físico Animal , Animais , Masculino , Atividade Motora , Proteína Básica da Mielina/metabolismo , Ratos Wistar , Sinaptofisina/metabolismo , Ganho de Peso
18.
Mol Med Rep ; 19(5): 3441-3448, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30816533

RESUMO

Ataxia­telangiectasia (A­T) is an autosomal recessive chromosome breakage disorder caused by mutations in the ATM serine/threonine kinase (ATM) gene. Typically, it presents in early childhood with progressive cerebellar dysfunction, accompanied by immunodeficiency and oculocutaneous telangiectasia. In the present study, the clinical and genetic findings of a Chinese family affected with A­T in two live siblings, the proband (II­2) and his elder brother (II­1), as well as a fetus (II­3) were reported. General health, clinical neurological, electrophysiological (motor and sensory nerve conduction) and magnetic resonance imaging evaluations revealed that patients II­1 and II­2 had similar symptoms of ataxia, dysarthria, conjunctival hyperemia and elevated serum α­fetoprotein, whereas patient II­1 had earlier A­T onset at 2 years old and more serious problems with movement and intelligence. Targeted sequencing followed by Sanger sequencing revealed that these two patients carried the compound heterozygotes of a novel nonsense mutation c.5170G>T (p.Glu1724Ter) and a known nonsense mutation c.748C>T (p.Arg250Ter) in the ATM gene. Each mutation was inherited from an asymptomatic parent, which therefore confirmed the diagnosis of A­T. Given this, proband's mother performed prenatal diagnosis in her third pregnancy. Unfortunately, the fetus had the same causal mutations as its siblings and the pregnancy was terminated. The findings of the present study expanded the mutation spectrum of the ATM gene and may help in understanding the genetic basis of A­T, in order to guide genetic counseling and prenatal diagnosis.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/genética , Ataxia Telangiectasia/diagnóstico , Ataxia Telangiectasia/genética , Estudos de Associação Genética , Aconselhamento Genético , Mutação , Fenótipo , Alelos , Grupo com Ancestrais do Continente Asiático , Ataxia Telangiectasia/fisiopatologia , Biomarcadores , Cerebelo/patologia , Biologia Computacional , Análise Mutacional de DNA , Eletromiografia , Feminino , Genótipo , Humanos , Imagem por Ressonância Magnética , Masculino , Linhagem , Avaliação de Sintomas
19.
Brain Dev ; 41(6): 551-554, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30850156

RESUMO

BACKGROUND: Rhinovirus is a common respiratory pathogen for children throughout the year; nevertheless, its central nervous system involvement is extremely rare, and only two cases have been reported to date: meningitis and sepsis-like illness. PATIENT: A previously healthy 2-year-old Japanese boy developed fever, followed by seizures and lethargy. His cerebrospinal fluid cell count and protein level were slightly increased; brain magnetic resonance imaging showed abnormal intensities in the bilateral cerebellar dentate nuclei, which were prominent in diffusion-weighted images. After his consciousness disturbance improved, cerebellar dysfunction became apparent. He was treated symptomatically, without steroids or any other immunosuppressants. He almost recovered within a few months; however, cerebellar atrophy became evident on brain magnetic resonance imaging. Using acute specimens, human rhinovirus A was detected in his throat swab and cerebrospinal fluid. DISCUSSION: Acute cerebellitis, in which cerebellar inflammation is predominant, is occasionally accompanied by cerebral symptoms, such as consciousness disturbance and seizures. As a causative pathogen, rotavirus is the most common; however, rhinovirus-associated acute encephalitis/encephalopathy and concurrent cerebellitis have not been reported before. Further research, using recent molecular techniques to detect various central nervous system pathogens, including rhinovirus, is needed to delineate the underlying pathophysiology.


Assuntos
Enterovirus/patogenicidade , Encefalite Infecciosa/etiologia , Encefalite Infecciosa/fisiopatologia , Encefalopatias/complicações , Sistema Nervoso Central/virologia , Doenças Cerebelares/patologia , Cerebelo/patologia , Pré-Escolar , Imagem de Difusão por Ressonância Magnética/métodos , Encefalite/patologia , Febre/complicações , Humanos , Japão , Masculino , Rhinovirus/patogenicidade , Rotavirus/patogenicidade , Infecções por Rotavirus/complicações , Convulsões/complicações
20.
Int Immunopharmacol ; 70: 302-312, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30852286

RESUMO

In the central nervous system (CNS), neuroinflammation, especially that modulated by the cell response of astrocytes and microglia, is associated with damage to neurons in neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and, Multiple Sclerosis. Lupeol is a dietary triterpene that has demonstrated biological activities as antioxidant. This study investigated the anti-inflammatory and neuroprotective effects of lupeol in an in vitro model of neuroinflammation in primary cerebellar cultures. Cultures were obtained from 6-day-old Wistar rats, subjected to inflammatory damage with lipopolysaccharide (LPS, 1 µg/mL) and treated with lupeol (0.1 µM). We observed, after a 48-hour treatment, through Fluorjade-B staining and immunocytochemistry (ICQ) for ßIII-tubulin, that lupeol induced neuroprotection in cultures submitted to inflammatory damage. On the other hand, through ICQ for GFAP, it was possible to observe that lupeol modulated the astrocyte morphology for Bergmann glia-like phenotype and, especially for velate astrocyte-like phenotype, both phenotypes associated with the neuroprotective profile. Moreover, RT-qPCR analysis showed that lupeol induced the down-regulation of the mRNA expression for proinflammatory markers TNF, iNOS and NLRP3, as well as the production of nitric oxide (method of Greiss), which were up-regulated by LPS, and also induced up-regulation of the mRNA expression for arginase and IL-6 mRNA. In addition, lupeol induced up-regulation of mRNA expression for neurotrophins GDNF and NGF and also for the sonic hedgehog-Gli pathway. Together, these results lead to the conclusion that lupeol inhibits neuroinflammation in cerebellar cultures and induces neuroprotection associated with the modulation of astrocyte response and expression of neurotrophic and inflammatory factors.


Assuntos
Anti-Inflamatórios/farmacologia , Astrócitos/fisiologia , Cerebelo/patologia , Inflamação Neurogênica/tratamento farmacológico , Triterpenos Pentacíclicos/farmacologia , Animais , Astrócitos/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Regulação da Expressão Gênica , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolissacarídeos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fatores de Crescimento Neural/metabolismo , Inflamação Neurogênica/imunologia , Neuroproteção , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Wistar , Tubulina (Proteína)/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
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