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2.
Stroke ; 51(1): 149-153, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31679502

RESUMO

Background and Purpose- Studies on the prevalence and risk factors of white matter lesions (WMLs) in Tibetans living at high altitudes are scarce. We conducted this study to determine the prevalence and risks of WMLs in Tibetan patients without or with nonacute stroke. Methods- We undertook a retrospective analysis of medical records of patients treated at the People's Hospital of Tibetan Autonomous Region and identified a total of 301 Tibetan patients without acute stroke. WML severity was graded by the Fazekas Scale. We assessed the overall and age-specific prevalence of WMLs and analyzed associations between WMLs and related factors with univariate and multivariate methods. Results- Of the 301 patients, 87 (28.9%) had peripheral vertigo, 83 (27.3%) had primary headache, 52 (17.3%) had a history of stroke, 36 (12.0%) had an anxiety disorder, 29 (9.6%) had epilepsy, 12 (4.0%) had infections of the central nervous system, and 3 (1.0%) had undetermined diseases. WMLs were present in 245 (81.4%) patients, and 54 (17.9%) were younger than 40 years. Univariate analysis showed that age, history of cerebral infarction, hypertension, the thickness of the common carotid artery intima, and plaque within the intracarotid artery were related risks for WMLs. Ordered logistic analysis showed that age, history of cerebral ischemic stroke, hypertension, male sex, and atrial fibrillation were associated with WML severity. Conclusions- Risk factors for WMLs appear similar for Tibetans residing at high altitudes and individuals living in the plains. Further investigations are needed to determine whether Tibetans residing at high altitudes have a higher burden of WMLs than inhabitants of the plains.


Assuntos
Infecções do Sistema Nervoso Central , Cefaleia , Vertigem , Substância Branca/fisiologia , Doença Aguda , Adulto , Fatores Etários , Idoso , Infecções do Sistema Nervoso Central/epidemiologia , Infecções do Sistema Nervoso Central/patologia , Feminino , Cefaleia/epidemiologia , Cefaleia/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/patologia , Tibet/epidemiologia , Vertigem/epidemiologia , Vertigem/patologia
3.
Eur J Clin Microbiol Infect Dis ; 38(11): 2177-2184, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31372902

RESUMO

The aim of this study was to analyze the clinical and laboratory characteristics of children with peripheral facial nerve palsy (pFP) with a focus on identifying infectious etiology and long-term outcome. We conducted an ICD-10-based retrospective chart review on children hospitalized with pFP between January 1, 2006, and December 31, 2016. Furthermore, a telephone-based follow-up survey was performed. A total of 158 patients were identified, with a median age of 10.9 years (interquartile range 6.4-13.7). An infectious disease was associated with pFP in 82 patients (51.9%); 73 cases were classified as idiopathic pFP (46.2%). Three cases occurred postoperatively or due to a peripheral tumor. Among the infectious diseases, we identified 33 cases of neuroborreliosis and 12 viral infections of the central nervous system (CNS), caused by the varicella-zoster virus, human herpesvirus 6, herpes simplex virus, enterovirus, and Epstein-Barr virus. Other infections were mainly respiratory tract infections (RTIs; 37 cases). Children with an associated CNS infection had more often headache and nuchal rigidity, a higher cerebrospinal fluid cell count, and a longer length of hospital stay. Long-term follow-up revealed an associated lower risk of relapse in CNS infection-associated pFP. Among all groups, permanent sequelae were associated with female sex, a shorter length of hospitalization, and a lower white blood cell count at presentation. pFP is frequently caused by an CNS infection or is associated with concurrent RTIs, with a potential impact on the short- and long-term clinical course.


Assuntos
Infecções do Sistema Nervoso Central/complicações , Paralisia Facial/etiologia , Infecções Respiratórias/complicações , Adolescente , Paralisia de Bell/complicações , Paralisia de Bell/patologia , Paralisia de Bell/fisiopatologia , Borrelia/isolamento & purificação , Infecções do Sistema Nervoso Central/líquido cefalorraquidiano , Infecções do Sistema Nervoso Central/patologia , Infecções do Sistema Nervoso Central/fisiopatologia , Líquido Cefalorraquidiano/citologia , Líquido Cefalorraquidiano/microbiologia , Líquido Cefalorraquidiano/virologia , Criança , Paralisia Facial/líquido cefalorraquidiano , Paralisia Facial/patologia , Paralisia Facial/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Infecções Respiratórias/líquido cefalorraquidiano , Infecções Respiratórias/patologia , Infecções Respiratórias/fisiopatologia , Estudos Retrospectivos , Estações do Ano , Vírus/isolamento & purificação
4.
Surg Infect (Larchmt) ; 20(6): 460-464, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30942663

RESUMO

Background: Post-operative central nervous system infection (PCNSI) caused by multi-drug-resistant/extensively drug-resistant (MDR/XDR) Acinetobacter baumannii is a severe complication. This study aimed to analyze the clinical presentation and treatment of this disorder. Patients and Methods: A retrospective study that recruited patients having PCNSI caused by MDR/XDR Acinetobacter baumannii was performed at our institute. The patients' demographic information and clinical data were recorded and analyzed. To analyze treatment, we assigned patients to different groups according to whether they had intraventricular/intrathecal injection of antibiotic agents or cerebrospinal fluid (CSF) drainage therapy. Results: Twenty-four patients were included. The risk factors were classified into two categories: environmental factors (intensive care unit stay, tracheal intubation or tracheotomy, positive culture of MDR/XDR Acinetobacter baumannii from other samples) or infectious approaches (CSF drainage, incision CSF leakage). Cerebrospinal fluid sterilization was achieved in 13 patients (54.2%) and the 30-day mortality was 50%. In the seven patients having intraventricular/intrathecal injection of antibiotic agents, the CSF sterilization rate was 71.4% (5/7) and 30-day mortality was 28.6% (2/7), compared with 47.1% (8/17; p = 0.27) and 58.8% (10/17; p = 0.18) in patients having only intravenous antibiotic agents. In 19 patients having CSF drainage therapy for PCNSI, the CSF sterilization rate was 63.2% (12/19) and 30-day mortality was 42.1% (8/19) compared with 20% (1/5; p = 0.08) and 80% (4/5; p = 0.13) in the remaining patients. Conclusions: The risk factors for PCNSI caused by Acinetobacter baumannii can be classified in two categories: environmental factors or infectious approaches. Both intraventricular/intrathecal injection of antibiotic agents and CSF drainage are helpful for CSF sterilization.


Assuntos
Infecções por Acinetobacter/patologia , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/uso terapêutico , Infecções do Sistema Nervoso Central/patologia , Farmacorresistência Bacteriana Múltipla , Procedimentos Neurocirúrgicos/efeitos adversos , Infecção da Ferida Cirúrgica/patologia , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções do Sistema Nervoso Central/tratamento farmacológico , Infecções do Sistema Nervoso Central/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/mortalidade , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
5.
Surg Infect (Larchmt) ; 20(4): 292-297, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30785859

RESUMO

Background: Intra-cranial infection with Acinetobacter baumannii is a tough problem because of the presence of multi-resistance and poor drug penetration through the blood-brain barrier. Such intra-cranial infections can lead to serious complications and death. We retrospectively analyzed the culture results and clinical characteristics of patients with intra-cranial infections in our hospital and suggested intravenous (IV) meropenem and intra-thecal (IT) amikacin therapy may be effective in the management of A. baumannii infection. Case presentation: We reported four cases of post-neuro-surgical A. baumannii intra-cranial infection whose clinical futures were high fever and consciousness disturbance. Our patients were treated successfully with IV meropenem and IT amikacin. Conclusion: We presented our cases of pandrug-resistant A. baumannii intra-cranial infection that was managed successfully with a systemic provision of IV meropenem and IT amikacin. Therefore, these cases exemplify that systemic administration of IV meropenem and IT amikacin can be a good therapeutic option against A. baumannii intra-cranial infection when colistin is not available.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Amicacina/administração & dosagem , Antibacterianos/administração & dosagem , Infecções do Sistema Nervoso Central/tratamento farmacológico , Meropeném/administração & dosagem , Procedimentos Neurocirúrgicos/efeitos adversos , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecções por Acinetobacter/patologia , Acinetobacter baumannii/isolamento & purificação , Administração Intravenosa , Adulto , Idoso , Infecções do Sistema Nervoso Central/patologia , Feminino , Humanos , Injeções Espinhais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/patologia , Resultado do Tratamento
6.
Rev Med Virol ; 29(1): e2021, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30548722

RESUMO

Owing to the large-scale epidemic of Zika virus disease and its association with microcephaly, properties that allow flaviviruses to cause nervous system diseases are an important area of investigation. At present, although potential pathogenic mechanisms of flaviviruses in the nervous system have been examined, they have not been completely elucidated. In this paper, we review the possible mechanisms of blood-brain barrier penetration, the pathological effects on neurons, and the association between virus mutations and neurotoxicity. A hypothesis on neurotoxicity caused by the Zika virus is presented. Clarifying the mechanisms of virulence of flaviviruses will be helpful in finding better antiviral drugs and optimizing the treatment of symptoms.


Assuntos
Pesquisa Biomédica/tendências , Infecções do Sistema Nervoso Central/patologia , Infecções do Sistema Nervoso Central/fisiopatologia , Infecções por Flavivirus/patologia , Infecções por Flavivirus/fisiopatologia , Flavivirus/patogenicidade , Humanos , Virulência
7.
Pediatr Infect Dis J ; 38(5): e99-e104, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30001229

RESUMO

A 4-year-old former 24-week gestation male and an 18-month-old former 26-week gestation female, both with history of intraventricular hemorrhage resulting in hydrocephalus, presented with Mycobacterium abscessus ventricular shunt infections affecting both the shunt track and the ventricular fluid. Both children required prolonged combination antimycobacterial therapy; the 4 years old required more than 2 months of triple intravenous antibiotics and intraventricular amikacin to sterilize the cerebrospinal fluid. Each infection came under control only after removal of all foreign material and multiple and extensive adjunctive surgical procedures to excise infected shunt track tissue. Central nervous system infections caused by M. abscessus are rare, and their management is challenging: prolonged antimicrobial therapy is required, adverse effects from antibiotics are common and rates of mortality and morbidity are high.


Assuntos
Infecções do Sistema Nervoso Central/diagnóstico , Infecções do Sistema Nervoso Central/patologia , Derivações do Líquido Cefalorraquidiano/efeitos adversos , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/patologia , Mycobacterium abscessus/isolamento & purificação , Antibacterianos/administração & dosagem , Infecções do Sistema Nervoso Central/tratamento farmacológico , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Resultado do Tratamento
8.
Clin Radiol ; 73(12): 999-1013, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30122607

RESUMO

Diffusion-weighted imaging (DWI) is a well-established technique in neuroimaging, but the diagnostic value of DWI outside the setting of acute infarct and abscess is sometimes under-recognised particularly in paediatric neuroimaging. DWI also plays an important role in the evaluation of intracranial infection, brain tumours, demyelinating diseases, and metabolic disorders. DWI can assist in the early detection and characterisation of intraocular and skull-base pathology. The cases presented in this article demonstrate the utility of DWI in paediatric neuroimaging. DWI can improve diagnostic sensitivity and in conjunction with other magnetic resonance imaging (MRI) sequences can aid in early diagnosis and management. Obtaining an early diagnosis may avoid potential complications and improve patient outcome.


Assuntos
Encefalopatias/diagnóstico por imagem , Infecções do Sistema Nervoso Central/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Doenças Metabólicas/diagnóstico por imagem , Neuroimagem , Encefalopatias/patologia , Infecções do Sistema Nervoso Central/patologia , Criança , Diagnóstico Precoce , Humanos , Doenças Metabólicas/patologia , Sensibilidade e Especificidade
9.
J Clin Microbiol ; 56(11)2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30135235

RESUMO

Health care- and device-associated central nervous system (CNS) infections have a distinct epidemiology, pathophysiology, and microbiology that require a unique diagnostic approach. Most clinical signs, symptoms, and tests used to diagnose community-acquired CNS infections are insensitive and nonspecific in neurosurgical patients due to postsurgical changes, invasive devices, prior antimicrobial exposure, and underlying CNS disease. The lack of a standardized definition of infection or diagnostic pathway has added to this challenge. In this review, we summarize the epidemiology, microbiology, and clinical presentation of these infections, discuss the issues with existing microbiologic tests, and give an overview of the current diagnostic approach.


Assuntos
Infecções do Sistema Nervoso Central/diagnóstico , Infecção Hospitalar/diagnóstico , Infecções Relacionadas à Prótese/diagnóstico , Algoritmos , Biomarcadores/líquido cefalorraquidiano , Infecções do Sistema Nervoso Central/líquido cefalorraquidiano , Infecções do Sistema Nervoso Central/microbiologia , Infecções do Sistema Nervoso Central/patologia , Infecção Hospitalar/líquido cefalorraquidiano , Infecção Hospitalar/microbiologia , Infecção Hospitalar/patologia , Testes Diagnósticos de Rotina , Humanos , Técnicas Microbiológicas , Procedimentos Neurocirúrgicos/efeitos adversos , Próteses e Implantes/efeitos adversos , Infecções Relacionadas à Prótese/líquido cefalorraquidiano , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/patologia
10.
Childs Nerv Syst ; 34(10): 1967-1971, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29961084

RESUMO

Hydatid disease of the central nervous system is rare and comprises about 2-3% of all the hydatid cyst cases reported in the world. Spinal hydatid is still rare. It is endemic in sheep and cattle-raising regions, seen mainly in Mediterranean countries including Turkey and Syria. Pediatric neurosurgeons in nonendemic countries face a challenge when they are encountered with hydatid cyst of the central nervous system due to lack of awareness and diagnostic dilemmas. It is also a mammoth economic problem in developing countries due to improper hygiene and lack of dedicated veterinary practice. The clinical features are largely nonspecific. However, with the advent of MR imaging, the diagnostic accuracy has increased. Intact removal of the cyst without causing any spillage is the goal and key to cure. In this manuscript, the current literature on hydatid cyst of the brain and spine is reviewed to understand the epidemiological, diagnostic accuracy and advances in therapeutics. A heightened clinical suspicion about hydatid disease, role of MR imaging and improving surgical strategies is discussed. A nationwide prevention of the disease is the ultimate goal.


Assuntos
Infecções do Sistema Nervoso Central/diagnóstico , Infecções do Sistema Nervoso Central/patologia , Equinococose/diagnóstico , Equinococose/patologia , Infecções do Sistema Nervoso Central/terapia , Equinococose/terapia , Humanos
11.
Jpn J Infect Dis ; 71(5): 338-342, 2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-29848841

RESUMO

While we previously detected anti-bornavirus antibodies via radioligand assay in psychiatric patients, we did not examine the viral pathogenicity in these individuals. Herein, we present 2 psychiatric patients who were seropositive for bornavirus and whose treatment-resistant symptoms improved after oral administration of ribavirin, a broad-spectrum antiviral agent. Cerebrospinal fluid analysis indicated that ribavirin affected the central nervous system of these patients. Ribavirin ameliorated intermittent involuntary head shaking, which is reminiscent of a symptom observed in bornavirus-infected animals. Using radioligand assays to examine the serial sera of these patients, we found a relationship between the titers of anti-bornavirus antibodies and the change in the patients' symptoms. Our findings suggest there is a relationship between bornavirus infection and human symptoms and that ribavirin may be useful in suppressing chronic bornavirus infection in some neuropsychiatric patients. However, the possibility remains that some other known or unknown virus other than bornavirus that is sensitive to ribavirin may have caused the symptoms. Additional evidence that directly indicates the causative relationship between bornavirus infection and human symptoms is needed before establishing the pathogenesis and treatment for human bornavirus infection.


Assuntos
Antivirais/administração & dosagem , Bornaviridae/isolamento & purificação , Infecções do Sistema Nervoso Central/diagnóstico , Infecções do Sistema Nervoso Central/tratamento farmacológico , Infecções por Mononegavirales/diagnóstico , Infecções por Mononegavirales/tratamento farmacológico , Ribavirina/administração & dosagem , Administração Oral , Adulto , Anticorpos Antivirais/sangue , Infecções do Sistema Nervoso Central/patologia , Feminino , Humanos , Masculino , Infecções por Mononegavirales/patologia , Resultado do Tratamento
12.
Viruses ; 10(6)2018 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-29914165

RESUMO

Tick-borne flaviviruses have a global distribution and cause significant human disease, including encephalitis and hemorrhagic fever, and often result in neurologic sequelae. There are two distinct properties that determine the neuropathogenesis of a virus. The ability to invade the central nervous system (CNS) is referred to as the neuroinvasiveness of the agent, while the ability to infect and damage cells within the CNS is referred to as its neurovirulence. Examination of laboratory variants, cDNA clones, natural isolates with varying pathogenicity, and virally encoded immune evasion strategies have contributed extensively to our understanding of these properties. Here we will review the major viral determinants of virulence that contribute to pathogenesis and influence both neuroinvasiveness and neurovirulence properties of tick-borne flaviviruses, focusing particularly on the envelope protein (E), nonstructural protein 5 (NS5), and the 3′ untranslated region (UTR).


Assuntos
Infecções do Sistema Nervoso Central/patologia , Infecções do Sistema Nervoso Central/virologia , Flavivirus/genética , Flavivirus/patogenicidade , Carrapatos/virologia , Fatores de Virulência/genética , Animais , Flavivirus/isolamento & purificação , Humanos
13.
Cell Microbiol ; 20(9): e12858, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29749044

RESUMO

Central nervous system (CNS) infection by Mycobacterium tuberculosis is one of the most devastating complications of tuberculosis, in particular in early childhood. In order to induce CNS infection, M. tuberculosis needs to cross specialised barriers protecting the brain. How M. tuberculosis crosses the blood-brain barrier (BBB) and enters the CNS is not well understood. Here, we use transparent zebrafish larvae and the closely related pathogen Mycobacterium marinum to answer this question. We show that in the early stages of development, mycobacteria rapidly infect brain tissue, either as free mycobacteria or within circulating macrophages. After the formation of a functionally intact BBB, the infiltration of brain tissue by infected macrophages is delayed, but not blocked, suggesting that crossing the BBB via phagocytic cells is one of the mechanisms used by mycobacteria to invade the CNS. Interestingly, depletion of phagocytic cells did not prevent M. marinum from infecting the brain tissue, indicating that free mycobacteria can independently cause brain infection. Detailed analysis showed that mycobacteria are able to cause vasculitis by extracellular outgrowth in the smaller blood vessels and by infecting endothelial cells. Importantly, we could show that this second mechanism is an active process that depends on an intact ESX-1 secretion system, which extends the role of ESX-1 secretion beyond the macrophage infection cycle.


Assuntos
Barreira Hematoencefálica/microbiologia , Infecções do Sistema Nervoso Central/patologia , Interações Hospedeiro-Patógeno , Infecções por Mycobacterium não Tuberculosas/patologia , Mycobacterium marinum/crescimento & desenvolvimento , Animais , Encéfalo/microbiologia , Modelos Animais de Doenças , Macrófagos/microbiologia , Peixe-Zebra
14.
Epidemiol Infect ; 146(6): 788-798, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29526169

RESUMO

Enterovirus A-71 (EV-A71) may be fatal, but the natural history, symptoms, and signs are poorly understood. This study aimed to examine the natural history of fatal EV-A71 infection and to identify the symptoms and signs of early warning of deterioration. This was a clinical observational study of fatal cases of EV-A71 infection treated at five Chinese hospitals between 1 January 2010 and 31 December 2012. We recorded and analysed 91 manifestations of EV-A71 infection in order to identify early prognosis indicators. There were 54 fatal cases. Median age was 21.5 months (Q1-Q3: 12-36). The median duration from onset to death was 78.5 h (range, 6 to 432). The multilayer perceptron analysis showed that ataxia respiratory, ultrahyperpyrexia, excessive tachycardia, refractory shock, absent pharyngeal reflex, irregular respiratory rhythm, hyperventilation, deep coma, pulmonary oedema and/or haemorrhage, excessive hypertension, tachycardia, somnolence, CRT extension, fatigue or sleepiness and age were associated with death. Autopsy findings (n = 2) showed neuronal necrosis, softening, perivascular cuffing, colloid and neuronophagia phenomenon in the brainstem. The fatal cases of enterovirus A71 had neurologic involvement, even at the early stage. Direct virus invasion through the neural pathway and subsequent brainstem damage might explain the rapid progression to death.


Assuntos
Infecções do Sistema Nervoso Central/mortalidade , Infecções do Sistema Nervoso Central/patologia , Enterovirus Humano A/isolamento & purificação , Infecções por Enterovirus/mortalidade , Infecções por Enterovirus/patologia , Adolescente , Infecções do Sistema Nervoso Central/epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Progressão da Doença , Infecções por Enterovirus/epidemiologia , Feminino , Humanos , Lactente , Masculino , Prognóstico , Fatores de Tempo
15.
New Microbiol ; 41(2): 165-167, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29384559

RESUMO

Brucellosis is the most common zoonosis in the world and it is caused by ingestion of foods contaminated by Brucella spp. that is able to avoid the immune system and can involve every organ system. The bacteria may affect the Central Nervous System (CNS) directly or using phagocytic cells with the way of the "Trojan Horse Model". Meningitis is the most common form of neuro-brucellosis (NB) but other neurological manifestation, with variable onset, such as severe encephalic involvement, neuropathy, vascular damage, radiculitis and hydrocephalus might happened. NB may manifest itself with an acute or chronic onset and could be the only manifestation of the infection or appearance during the systemic disease. Frequently the diagnosis might be very difficult and the clinical characteristics and the microbiological demonstration in the blood and in the CSF are necessary. The prognosis of brucella meningitis is generally better than other forms of chronic meningitis except for encephalitis or spinal cord involvement. The treatment is based on the combination of two or three antibiotics to achieve normalization of the cerebrospinal fluid parameters otherwise relapse are relatively frequent. We describe an atypical case of brucellar meningitis with many stroke-like signs, think as recurrent cerebrovascular events and treated with antithrombotic therapy, but without meningeal syndrome.


Assuntos
Brucelose/microbiologia , Brucelose/patologia , Infecções do Sistema Nervoso Central/microbiologia , Infecções do Sistema Nervoso Central/patologia , Antibacterianos/uso terapêutico , Brucelose/tratamento farmacológico , Infecções do Sistema Nervoso Central/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade
16.
J Virol ; 92(7)2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29321331

RESUMO

Sindbis virus (SINV) infection of neurons in the brain and spinal cord in mice provides a model system for investigating recovery from encephalomyelitis and antibody-mediated clearance of virus from the central nervous system (CNS). To determine the roles of IgM and IgG in recovery, we compared the responses of immunoglobulin-deficient activation-induced adenosine deaminase-deficient (AID-/-), secretory IgM-deficient (sIgM-/-), and AID-/- sIgM-/- double-knockout (DKO) mice with those of wild-type (WT) C57BL/6 mice for disease, clearance of infectious virus and viral RNA from brain and spinal cord, antibody responses, and B cell infiltration into the CNS. Because AID is essential for immunoglobulin class switch recombination and somatic hypermutation, AID-/- mice produce only germ line IgM, while sIgM-/- mice secrete IgG but no IgM and DKO mice produce no secreted immunoglobulin. After intracerebral infection with the TE strain of SINV, most mice recovered. Development of neurologic disease occurred slightly later in sIgM-/- mice, but disease severity, weight loss, and survival were similar between the groups. AID-/- mice produced high levels of SINV-specific IgM, while sIgM-/- mice produced no IgM and high levels of IgG2a compared to WT mice. All mice cleared infectious virus from the spinal cord, but DKO mice failed to clear infectious virus from brain and had higher levels of viral RNA in the CNS late after infection. The numbers of infected cells and the amount of cell death in brain were comparable. We conclude that antibody is required and that either germ line IgM or IgG is sufficient for clearance of virus from the CNS.IMPORTANCE Mosquito-borne alphaviruses that infect neurons can cause fatal encephalomyelitis. Recovery requires a mechanism for the immune system to clear virus from infected neurons without harming the infected cells. Antiviral antibody has previously been shown to be a noncytolytic means for alphavirus clearance. Antibody-secreting cells enter the nervous system after infection and produce antiviral IgM before IgG. Clinical studies of human viral encephalomyelitis suggest that prompt production of IgM is associated with recovery, but it was not known whether IgM is effective for clearance. Our studies used mice deficient in production of IgM, IgG, or both to characterize the antibody necessary for alphavirus clearance. All mice developed similar signs of neurologic disease and recovered from infection. Antibody was necessary for virus clearance from the brain, and either early germ line IgM or IgG was sufficient. These studies support the clinical observation that prompt production of antiviral antibody is a determinant of outcome.


Assuntos
Infecções por Alphavirus/imunologia , Anticorpos Antivirais/imunologia , Encéfalo/imunologia , Infecções do Sistema Nervoso Central/imunologia , Imunoglobulina M/imunologia , Vírus Sindbis/imunologia , Infecções por Alphavirus/genética , Infecções por Alphavirus/patologia , Animais , Anticorpos Antivirais/genética , Encéfalo/patologia , Encéfalo/virologia , Linhagem Celular , Infecções do Sistema Nervoso Central/genética , Infecções do Sistema Nervoso Central/patologia , Cricetinae , Citidina Desaminase/deficiência , Feminino , Imunoglobulina M/genética , Camundongos , Camundongos Knockout , Vírus Sindbis/genética
17.
Am J Med ; 131(1): 25-32, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28889928

RESUMO

Microorganisms can affect the entire neuraxis, producing a variety of neurologic complications that frequently entail prolonged hospitalizations and complicated treatment regimens. The spread of pathogens to new regions and the reemergence of opportunistic organisms in immunocompromised patients pose increasing challenges to health care professionals. Because rapid diagnosis and treatment may prevent long-term neurologic sequelae, providers should approach these diseases with a structured, neuroanatomic framework, incorporating a thorough history, examination, laboratory analysis, and neuroimaging in their clinical reasoning and decision-making.


Assuntos
Infecções do Sistema Nervoso Central/diagnóstico , Infecções do Sistema Nervoso Central/patologia , Doenças do Sistema Nervoso Periférico/microbiologia , Humanos , Hospedeiro Imunocomprometido , Transmissão de Doença Infecciosa do Paciente para o Profissional , Infecções Oportunistas , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/microbiologia , Acidente Vascular Cerebral/patologia
18.
Am J Physiol Cell Physiol ; 314(2): C152-C165, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29070490

RESUMO

The choroid plexus (CP) is responsible for the production of a large amount of the cerebrospinal fluid (CSF). As a highly vascularized structure, the CP also presents a significant frontier between the blood and the central nervous system (CNS). To seal this border, the epithelium of the CP forms the blood-CSF barrier, one of the most important barriers separating the CNS from the blood. During the course of infectious disease, cells of the CP can experience interactions with intruding pathogens, especially when the CP is used as gateway for entry into the CNS. In return, the CP answers to these encounters with diverse measures. Here, we will review the distinct responses of the CP during infection of the CNS, which include engaging of signal transduction pathways, the regulation of gene expression in the host cells, inflammatory cell response, alterations of the barrier, and, under certain circumstances, cell death. Many of these actions may contribute to stage an immunological response against the pathogen and subsequently help in the clearance of the infection.


Assuntos
Barreira Hematoencefálica/metabolismo , Permeabilidade Capilar , Infecções do Sistema Nervoso Central/líquido cefalorraquidiano , Plexo Corióideo/irrigação sanguínea , Plexo Corióideo/metabolismo , Animais , Barreira Hematoencefálica/imunologia , Infecções do Sistema Nervoso Central/imunologia , Infecções do Sistema Nervoso Central/patologia , Plexo Corióideo/imunologia , Interações Hospedeiro-Patógeno , Humanos , Prognóstico , Transdução de Sinais
19.
Lancet Infect Dis ; 18(1): e1-e13, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28844634

RESUMO

Microcephaly is an important sign of neurological malformation and a predictor of future disability. The 2015-16 outbreak of Zika virus and congenital Zika infection brought the world's attention to links between Zika infection and microcephaly. However, Zika virus is only one of the infectious causes of microcephaly and, although the contexts in which they occur vary greatly, all are of concern. In this Review, we summarise important aspects of major congenital infections that can cause microcephaly, and describe the epidemiology, transmission, clinical features, pathogenesis, management, and long-term consequences of these infections. We include infections that cause substantial impairment: cytomegalovirus, herpes simplex virus, rubella virus, Toxoplasma gondii, and Zika virus. We highlight potential issues with classification of microcephaly and show how some infants affected by congenital infection might be missed or incorrectly diagnosed. Although Zika virus has brought the attention of the world to the problem of microcephaly, prevention of all infectious causes of microcephaly and appropriately managing its consequences remain important global public health priorities.


Assuntos
Infecções do Sistema Nervoso Central/congênito , Infecções do Sistema Nervoso Central/complicações , Gerenciamento Clínico , Microcefalia/epidemiologia , Microcefalia/etiologia , Infecções do Sistema Nervoso Central/epidemiologia , Infecções do Sistema Nervoso Central/patologia , Humanos , Microcefalia/diagnóstico , Microcefalia/patologia
20.
Int J Paleopathol ; 19: 111-118, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29198392

RESUMO

Trepanation is the scraping, cutting, or drilling of an opening (or openings) into the neurocranium. World surveys reveal that a number of ancient cultures experimented with cranial surgery, and that in some areas these practices continued into modern times. Archaeological discoveries of possible trepanations continue to be made, often from geographic areas or time periods from which the practice was not previously known. Unfortunately, most of these reports describe single crania with healed defects interpreted as trepanations. When evaluating a possible trepanation in a skull that lacks medical history or comes from an archaeological context where there is no other evidence that such operations were performed, a thorough differential diagnosis is essential. Identification of unhealed trepanations is a relatively straightforward exercise, since tool marks provide direct evidence of surgical intervention. A confident diagnosis is more difficult in healed defects of the skull, where the mechanism that produced an opening may be obscured by bone remodeling. There are many possible causes of defects of the skull vault, including congenital and developmental anomalies, trauma, infection, neoplasm, and taphonomic damage. For this reason, a careful differential diagnosis is essential for identifying surgical intervention and distinguishing it from cranial defects caused by other mechanisms.


Assuntos
Paleopatologia/métodos , Crânio , Trepanação , Neoplasias Encefálicas/história , Neoplasias Encefálicas/patologia , Infecções do Sistema Nervoso Central/história , Infecções do Sistema Nervoso Central/patologia , Traumatismos Craniocerebrais/história , Traumatismos Craniocerebrais/patologia , Anormalidades Craniofaciais/história , Anormalidades Craniofaciais/patologia , Diagnóstico Diferencial , História Antiga , Humanos , Osteogênese , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Crânio/anormalidades , Crânio/lesões , Crânio/patologia
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