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1.
BMC Infect Dis ; 20(1): 721, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004020

RESUMO

BACKGROUND: Listeria monocytogenes (L. monocytogenes) is a facultative intracellular bacterial pathogen which can invade different mammalian cells and reach to the central nervous system (CNS), leading to meningoencephalitis and brain abscesses. In the diagnosis of L. monocytogenes meningoencephalitis (LMM), the traditional test often reports negative owing to the antibiotic treatment or a low number of bacteria in the cerebrospinal fluid. To date, timely diagnosis and accurate treatment remains a challenge for patients with listeria infections. CASE PRESENTATION: We present the case of a 66-year-old woman whose clinical manifestations were suspected as tuberculous meningoencephalitis, but the case was finally properly diagnosed as LMM by next-generation sequencing (NGS). The patient was successfully treated using a combined antibacterial therapy, comprising ampicillin and trimethoprim-sulfamethoxazole. CONCLUSION: To improve the sensitivity of LMM diagnosis, we used NGS for the detection of L. monocytogenes. Hence, the clinical utility of this approach can be very helpful since it provides quickly and trust results.


Assuntos
Listeria monocytogenes/genética , Meningite por Listeria/microbiologia , Meningoencefalite/microbiologia , Idoso , Ampicilina/uso terapêutico , Antibacterianos/uso terapêutico , Abscesso Encefálico/tratamento farmacológico , Erros de Diagnóstico , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Listeria monocytogenes/isolamento & purificação , Meningite por Listeria/diagnóstico , Meningite por Listeria/tratamento farmacológico , Meningoencefalite/diagnóstico , Meningoencefalite/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Tuberculose Meníngea/diagnóstico , Tuberculose Meníngea/microbiologia
2.
BMJ Case Rep ; 13(9)2020 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-32895254

RESUMO

A 40-year-old man presented with altered mental status after a recenthospitalisation for COVID-19 pneumonia. Cerebrospinal fluid (CSF) analysis showed lymphocytosis concerning for viral infection. The CSF PCR for SARS-CoV-2 was negative, yet this could not exclude COVID-19 meningoencephalitis. During hospitalisation, the patient's mentation deteriorated further requiring admission to the intensive care unit (ICU). Brain imaging and electroencephalogram (EEG) were unremarkable. He was, thus, treated with intravenous immunoglobulin (IVIg) for 5 days with clinical improvement back to baseline. This case illustrates the importance of considering COVID-19's impact on the central nervous system (CNS). Haematogenous, retrograde axonal transport, and the effects of cytokine storm are the main implicated mechanisms of CNS entry of SARS-CoV-2. While guidelines remain unclear, IVIg may be of potential benefit in the treatment of COVID-19-associated meningoencephalitis.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Meningoencefalite/tratamento farmacológico , Meningoencefalite/etiologia , Pneumonia Viral/complicações , Adulto , Humanos , Masculino , Pandemias , Resultado do Tratamento
3.
BMC Infect Dis ; 20(1): 654, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894070

RESUMO

BACKGROUND: Brucellosis is a zoonotic disease caused by brucella. It has been an increasing trend in recent years (Wang H, Xu WM, Zhu KJ, Zhu SJ, Zhang HF, Wang J, Yang Y, Shao FY, Jiang NM, Tao ZY, Jin HY, Tang Y, Huo LL, Dong F, Li ZJ, Ding H, Liu ZG, Emerg Microbes Infect 9:889-99, 2020). Brucellosis is capable to invade multiple systems throughout the body, lacking in typical clinical manifestations, and easily misdiagnosed and mistreated. CASE PRESENTATION: We report a case of a male, 5-year-and-11-month old child without relevant medical history, who was admitted to hospital for 20 days of fever. When admitted to the hospital, we found that he was enervated, irritable and sleepy, accompanied with red eyes phenomenon. After anti-infection treatment with meropenem, no improvement observed. Lumbar puncture revealed normal CSF protein, normal cells, and negative culture. Later, doppler echocardiography suggested coronary aneurysms, and incomplete Kawasaki Disease with coronary aneurysms was proposed. The next day, brucellosis agglutination test was positive. Metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid suggested B.melitensis, which was confirmed again by blood culture. The child was finally diagnosed as brucellosis with meningocephalitis, coronary aneurysm and keratitis. According to our preliminary research and review, such case has never been reported in detail before. After diagnosis confirmation, the child was treated with rifampicin, compound sulfamethoxazole, and ceftriaxone for cocktail anti-infection therapy. Aspirin and dipyridamole were also applied for anticoagulant therapy. After medical treatment, body temperature of the child has reached normal level, eye symptoms alleviated, and mental condition gradually turned normal. Re-examination of the doppler echocardiographic indicated that the coronary aneurysm was aggravated, so warfarin was added for amplification of anticoagulation treatment. At present, 3 months of follow-up, the coronary artery dilatation gradually assuaged, and the condition is continued to alleviate. CONCLUSION: Brucellosis can invade nervous system, coronary artery, and cornea. Brucellosis lacks specific signs for clinical diagnosis. The traditional agglutination test and the new mNGS are convenient and effective, which can provide the reference for clinical diagnosis.


Assuntos
Brucella melitensis/isolamento & purificação , Brucelose/complicações , Brucelose/diagnóstico , Aneurisma Coronário/complicações , Aneurisma Coronário/diagnóstico , Ceratite/complicações , Ceratite/diagnóstico , Meningoencefalite/complicações , Meningoencefalite/diagnóstico , Testes de Aglutinação , Animais , Anti-Infecciosos/uso terapêutico , Anticoagulantes/uso terapêutico , Brucelose/tratamento farmacológico , Ceftriaxona/uso terapêutico , Pré-Escolar , Erros de Diagnóstico , Febre/tratamento farmacológico , Humanos , Ceratite/tratamento farmacológico , Masculino , Meningoencefalite/tratamento farmacológico , Rifampina/uso terapêutico , Sulfametoxazol/uso terapêutico , Resultado do Tratamento , Zoonoses/diagnóstico , Zoonoses/tratamento farmacológico
4.
Aust Vet J ; 98(10): 491-498, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32794230

RESUMO

OBJECTIVE: To analyse outcome in dogs with a presumptive diagnosis of meningoencephalomyelitis of unknown origin (MUO) treated with prednisolone and ciclosporin and to assess the effect of a number of patient variables on survival time and rate of relapse. DESIGN: Retrospective case series. METHODS: Medical records of 40 client-owned dogs with a diagnosis of MUO treated with prednisolone and ciclosporin at one institution between June 2010 and January 2018 were reviewed retrospectively to assess survival times and prognostic indicators for death and/or relapse. The minimum follow-up time was 11 months post-diagnosis. RESULTS: Median survival was 1345 days (95% confidence interval: 487-∞). No associations with hazard of death or relapse were detected for the presence of multifocal magnetic resonance imaging (MRI) abnormalities, caudal fossa location of MRI abnormalities, value of cerebrospinal fluid total nucleated cell count or total protein at time of diagnosis, or suspected elevation in intracranial pressure at time of diagnosis. CONCLUSION: Protracted survival time may be achieved with a treatment combination of prednisolone and ciclosporin. Suspected elevation in intracranial pressure at the time of diagnosis did not affect long-term outcome in this cohort.


Assuntos
Doenças do Cão/tratamento farmacológico , Meningoencefalite/tratamento farmacológico , Meningoencefalite/veterinária , Animais , Ciclosporina/uso terapêutico , Cães , Prednisolona/uso terapêutico , Recidiva , Estudos Retrospectivos
6.
mBio ; 10(6)2019 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796539

RESUMO

Cryptococcal meningitis is a lethal disease with few therapeutic options. Induction therapy with fluconazole has been consistently demonstrated to be associated with suboptimal microbiological and clinical outcomes. Exposure to fluconazole causes dynamic changes in antifungal susceptibility, which are associated with the development of aneuploidy. The implications of this phenomenon for pharmacodynamics of fluconazole for cryptococcal meningitis are poorly understood. The pharmacodynamics of fluconazole were studied using a hollow-fiber infection model (HFIM) and a well-characterized murine model of cryptococcal meningoencephalitis. The relationship between drug exposure and both antifungal killing and the emergence of resistance was quantified. The same relationships were further evaluated in a recently described group of patients with cryptococcal meningitis undergoing induction therapy with fluconazole at 800 to 1,200 mg/day. The pattern of emergence of fluconazole resistance followed an "inverted U." Resistance amplification was maximal and suppressed at ratios of the area under the concentration-time curve for the free, unbound fraction of the drug to the MIC (fAUC:MIC) of 34.5 to 138 and 305.6, respectively. Emergence of resistance was observed in vivo with an fAUC:MIC of 231.4. Aneuploidy with duplication of chromosome 1 was demonstrated to be the underlying mechanism in both experimental models. The pharmacokinetic (PK)-pharmacodynamic model accurately described the PK, antifungal killing, and emergence of resistance. Monte Carlo simulations from the clinical pharmacokinetic-pharmacodynamic model showed that only 12.8% of simulated patients receiving fluconazole at 1,200 mg/day achieved sterilization of the cerebrospinal fluid (CSF) after 2 weeks and that 83.4% had a persistent subpopulation that was resistant to fluconazole. Fluconazole is primarily ineffective due to the emergence of resistance. Treatment with 1,200 mg/day leads to the killing of a susceptible subpopulation but is compromised by the emergence of resistance.IMPORTANCE Cryptococcal meningitis is a lethal disease with few treatment options. The incidence remains high and intricately linked with the HIV/AIDS epidemic. In many parts of the world, fluconazole is the only agent that is available for the initial treatment of cryptococcal meningitis despite considerable evidence that it is associated with suboptimal microbiological and clinical outcomes. Fluconazole has a fungistatic mode of action: it predominantly inhibits growth rather than causing fungal killing. Our work shows that the pattern of fluconazole activity is caused by the emergence of resistance in Cryptococcus not detected by standard susceptibility tests, with chromosomal duplication/aneuploidy as the main mechanism. Resistance emergence is related to drug exposure and occurs with the use of clinically relevant regimens. Hence, fluconazole (and potentially other agents that target 14-alpha-demethylase) is compromised by an intrinsic property that limits its effectiveness. However, this resistance may be potentially overcome by dosage escalation or the use of combination therapy.


Assuntos
Antifúngicos/uso terapêutico , Farmacorresistência Fúngica/efeitos dos fármacos , Fluconazol/uso terapêutico , Meningite Criptocócica/tratamento farmacológico , Adulto , Animais , Cryptococcus neoformans/efeitos dos fármacos , Feminino , Humanos , Masculino , Meningoencefalite/tratamento farmacológico , Meningoencefalite/microbiologia , Camundongos , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade , Adulto Jovem
7.
Vet J ; 254: 105395, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31836169

RESUMO

Meningoencephalitis of unknown origin (MUO) is a common inflammatory disease of the central nervous system. Several studies investigated finding prognostic factors, but results are contradictory. The aim of this study was to determine the concentrations of blood lactate (Blood-L) and cerebrospinal fluid lactate (CSF-L) in dogs with MUO for prognostic purposes. A total of 45 dogs with MUO (MUO group) and 11 with idiopathic epilepsy (IE group) were included. In the MUO group, 22 dogs were treated with prednisolone + cytosine arabinoside, 17 with prednisolone ± cyclosporine, and six received no treatment. In the MUO group, there was a strong-moderate positive correlation between Blood-L and CSF-L (ρ = 0.63557; P < 0.0001), a strong-moderate negative correlation between survival and CSF-L (ρ= -0.50210; P < 0.0004), and a weak negative correlation between survival and Blood-L (ρ= -0.35685; P < 0.0220). Dogs with a favourable response to treatment at 1 month had lower initial concentrations of Blood-L and CSF-L (P < 0.0010; P < 0.0037), and those with a worse response had higher values (P < 0.0497; P < 0.0004). Dogs that remained stable with treatment showed lower CSF-L concentrations (P < 0.0013). Dogs with Blood-L>4 mmol/L (P < 0.03) and/or CSF-L> 4 mmol/L (P < 0.009) had lower survival rates with the latter also showing more severe signs, probably indicating severe neuronal damage. These findings suggest that concentrations of CSF-L and Blood-L in dogs with MUO could be used as prognostic indicators.


Assuntos
Doenças do Cão/sangue , Doenças do Cão/líquido cefalorraquidiano , Ácido Láctico/sangue , Ácido Láctico/líquido cefalorraquidiano , Meningoencefalite/veterinária , Animais , Anti-Inflamatórios/uso terapêutico , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Citarabina/uso terapêutico , Cães , Feminino , Masculino , Meningoencefalite/sangue , Meningoencefalite/líquido cefalorraquidiano , Meningoencefalite/tratamento farmacológico , Prednisolona/uso terapêutico , Prognóstico , Estudos Prospectivos
8.
Medicine (Baltimore) ; 98(51): e18070, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31860956

RESUMO

INTRODUCTION: In this study, we presented a rare case of Epstein-Barr virus (EBV) meningoencephalitis presented with meningoencephalitis-like symptoms and diffuse edematous hemorrhage. PATIENT CONCERNS: A 77-year-old male patient was admitted to our hospital with fever, headache, confusion, and unconsciousness for 7 days. Physical examination revealed unconsciousness and stiffness of the neck. DIAGNOSIS: The final diagnosis was EBV meningoencephalitis. INTERVENTIONS: Ganciclovir (two times 350 mg/day, 21 days), methylprednisolone sodium succinate (120 mg, 5 days), and IV immunoglobulins (IV Ig) (0.4 g/kg, 5 days) were given to this patient. OUTCOMES: But the patient's clinical symptoms did not improve, and he was still in a coma. His family refused to be further diagnosed and discharged. After discharge for 2 months, the patient was in a coma. Four months later, the patient died of complications of pulmonary infection. CONCLUSION: The patient is an adult, and imaging was dominated by intracranial diffuse microhemorrhage and edema, which was different from the typical imaging characteristics of EBV encephalitis as previously reported. This specific imaging change may provide new clinical value for the diagnosis of EBV encephalitis.


Assuntos
Infecções por Vírus Epstein-Barr/tratamento farmacológico , Ganciclovir/administração & dosagem , Imunoglobulinas Intravenosas/uso terapêutico , Imagem por Ressonância Magnética/métodos , Meningoencefalite/tratamento farmacológico , Metilprednisolona/administração & dosagem , Idoso , Quimioterapia Combinada , Infecções por Vírus Epstein-Barr/diagnóstico por imagem , Seguimentos , Humanos , Masculino , Meningoencefalite/diagnóstico por imagem , Meningoencefalite/virologia , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
9.
J Vet Intern Med ; 33(6): 2701-2708, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31549740

RESUMO

BACKGROUND: Cerebrospinal fluid (CSF) lactate is frequently used as a biomarker in humans with inflammatory central nervous system (CNS) disorders including bacterial meningitis and autoimmune disorders such as multiple sclerosis. HYPOTHESIS: Cerebrospinal fluid lactate concentrations are increased in a subset of dogs with inflammatory CNS disorders. ANIMALS: One hundred two client-owned dogs diagnosed with inflammatory CNS disease. METHODS: Case series. Cases were identified both prospectively at the time of diagnosis and retrospectively by review of a CSF biorepository. Cerebrospinal fluid lactate was analyzed with a commercially available, handheld lactate monitor. Subcategories of inflammatory disease were created for comparison (eg, steroid-responsive meningitis arteritis, meningoencephalitis of unknown etiology). RESULTS: Cerebrospinal fluid lactate concentrations were above reference range in 47% of dogs (median, 2.5 mmol/L; range, 1.0-11.7 mmol/L). There was no significant difference in lactate concentrations between disease subcategories (P = .48). Significant but weak correlations were noted between CSF lactate concentration and nucleated cell count (r = .33, P < .001), absolute large mononuclear cell count (r = .44, P < .001), absolute small mononuclear cell count (r = .39, P < .001), absolute neutrophil cell count (r = .24, P = .01), and protein (r = .44, P < .001). No correlation was found between CSF lactate concentration and CSF red blood cell count (P = .58). There was no significant association of CSF lactate concentration with survival (P = .27). CONCLUSIONS AND CLINICAL IMPORTANCE: Cerebrospinal fluid lactate concentrations could serve as a rapid biomarker of inflammatory CNS disease in dogs.


Assuntos
Doenças do Cão/líquido cefalorraquidiano , Inflamação/veterinária , Ácido Láctico/líquido cefalorraquidiano , Meningoencefalite/veterinária , Animais , Cães , Inflamação/líquido cefalorraquidiano , Meningoencefalite/líquido cefalorraquidiano , Meningoencefalite/tratamento farmacológico , Meningoencefalite/patologia , Valores de Referência , Estudos Retrospectivos , Esteroides/uso terapêutico
10.
J Vet Pharmacol Ther ; 42(6): 588-592, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31490575

RESUMO

The objective of this study was to evaluate the pharmacokinetics of the standard cytarabine (Ara-C) protocol (50 mg/m2 subcutaneously every 12 hr for 2 days) used for dogs with neuroinflammatory disease and compare it to two more practical protocols (a single 200 mg/m2 subcutaneous dose and two 100 mg/m2 subcutaneous doses every 12 hr). Four client-owned dogs previously diagnosed with meningoencephalomyelitis of unknown origin were administered three distinct Ara-C protocols with a 21-day washout between each protocol. A complete blood count was performed seven days after each dosing protocol to assess for clinically relevant myelosuppression. No adverse events were observed. Plasma Ara-C concentrations were measured using a validated liquid chromatography coupled to tandem mass spectrometry assay. The mean maximal concentrations in this study were 4,230, 9,293, and 16,675 ng/ml for a single dose of 50, 100, and 200 mg/m2 , respectively. There was a linear relationship between dose and drug exposure. Drug exposure was similar regardless of the dosing protocol when the total dose was analyzed, with an area under the concentration versus time curve of 37,026, 38,465, and 32,510 ng × hr/ml for 50, 100, and 200 mg/m2 , respectively.


Assuntos
Citarabina/farmacocinética , Citarabina/uso terapêutico , Doenças do Cão/tratamento farmacológico , Meningoencefalite/veterinária , Animais , Área Sob a Curva , Citarabina/administração & dosagem , Doenças do Cão/sangue , Cães , Relação Dose-Resposta a Droga , Feminino , Meia-Vida , Imunossupressores/administração & dosagem , Imunossupressores/farmacocinética , Imunossupressores/uso terapêutico , Injeções Subcutâneas , Masculino , Meningoencefalite/tratamento farmacológico
11.
BMC Infect Dis ; 19(1): 722, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31420023

RESUMO

BACKGROUND: Coccidioides spp. are dimorphic fungi endemic to Central America, regions of South America and southwestern USA. Two species cause most human disease: Coccidioides immitis (primarily California isolates) and Coccidioides posadasii. Coccidioidomycosis is typically acquired through inhalation of soil or dust containing spores. Coccidioidal meningitis (CM), most common in the immunocompromised host, can also affect immunocompetent hosts. CASE PRESENTATION: We report a case of C. posadasii meningoencephalitis in a previously healthy 42-year-old Caucasian male who returned to Canada after spending time working in New Mexico. He presented with a 3-week history of headache, malaise and low-grade fevers. He developed progressive confusion and decreasing level of consciousness following hospitalization. Evidence of hydrocephalus and leptomeningeal enhancement was demonstrated on magnetic resonance imaging (MRI) of his brain. Serologic and PCR testing of the patient's CSF confirmed Coccidioides posadasii. Despite appropriate antifungal therapy he continues to have significant short-term memory deficits and has not returned to his full baseline functional status. CONCLUSIONS: Travel to endemic regions can result in disease secondary to Coccidioides spp. and requires physicians in non-endemic areas to have a high index of suspicion. Effective therapeutic options have reduced the mortality rate of CM, however, it is still associated with significant morbidity and requires life-long therapy.


Assuntos
Antifúngicos/uso terapêutico , Coccidioidomicose/microbiologia , Meningite Fúngica/microbiologia , Meningoencefalite/microbiologia , Adulto , Antituberculosos/uso terapêutico , Encéfalo/diagnóstico por imagem , Encéfalo/microbiologia , Encéfalo/patologia , Canadá , Coccidioides/genética , Coccidioides/patogenicidade , Coccidioidomicose/tratamento farmacológico , Humanos , Imunocompetência , Imunoglobulina M/líquido cefalorraquidiano , Imagem por Ressonância Magnética , Masculino , Meningite Fúngica/diagnóstico por imagem , Meningite Fúngica/tratamento farmacológico , Meningoencefalite/tratamento farmacológico , New Mexico , Viagem
12.
Indian J Med Microbiol ; 37(1): 120-122, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31424023

RESUMO

Primary amoebic meningoencephalitis is rare but fatal disease encountered in immunocompetent individuals. Here, we present a case of a previously healthy 8-month-old female child, who presented with features of meningoencephalitis of 2 days' duration. Rapidly moving trophozoites of amoeba were observed in cerebrospinal fluid, which were confirmed to be Naegleria fowleri on polymerase chain reaction. Broad-spectrum antimicrobial therapy with ceftriaxone, vancomycin, amphotericin B and acyclovir was initiated. However, the patient deteriorated and left the hospital against medical advice. The isolation of N. fowleri in this case demands for increased awareness for prompt diagnosis and management in view of its high mortality.


Assuntos
Amebíase/diagnóstico , Amebicidas/uso terapêutico , Infecções Protozoárias do Sistema Nervoso Central/diagnóstico , Meningoencefalite/parasitologia , Naegleria fowleri/isolamento & purificação , Aciclovir/uso terapêutico , Amebíase/tratamento farmacológico , Anfotericina B/uso terapêutico , Ceftriaxona/uso terapêutico , Infecções Protozoárias do Sistema Nervoso Central/tratamento farmacológico , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Líquido Cefalorraquidiano/parasitologia , Feminino , Humanos , Lactente , Meningoencefalite/diagnóstico , Meningoencefalite/tratamento farmacológico , Naegleria fowleri/genética , Trofozoítos/isolamento & purificação , Vancomicina/uso terapêutico
13.
Medicine (Baltimore) ; 98(35): e16985, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464947

RESUMO

RATIONALE: Angiostrongylus cantonensis-induced eosinophilic meningoencephalitis (AEM) in infants is a very rare but fatal disease. Utilization of genetic assay to detect the cerebral parasite plays an important role for the treatment of the infection. PATIENT CONCERNS: Two infants (<2 years) presented with cough, intermittent fever, mental fatigue, and poor diet. DIAGNOSIS: The patients were under clinical examination and laboratory test including cardiac ultrasound, chest X-ray, blood or cerebrospinal fluid (CSF) cell counting, serum enzyme-linked immunosorbent assay (ELISA), head magnetic resonance imaging (MRI) and next-generation sequencing (NGS) on DNA from CSF. Due to hypereosinophils in patients' peripheral blood and CSF, and abundant DNA sequences from A cantonensis in CSF, the patients were diagnosed with Angiostrongylus eosinophilic meningoencephalitis. INTERVENTIONS: The patients were treated with albendazole to deworm, and methylprednisolone to reduce inflammation. OUTCOME: The patients were completely recovered from AEM without relapse after 10-day treatment. LESSONS: ELISA and MRI are not sufficiently accurate for the diagnosis of AEM in infants. NGS can specify the infection by the cerebral parasite and offers a new effective approach for the early and precise diagnosis of AEM in infants.


Assuntos
Eosinofilia/complicações , Meningoencefalite/complicações , Meningoencefalite/diagnóstico , Meningoencefalite/parasitologia , Infecções por Strongylida/diagnóstico , Albendazol/uso terapêutico , Angiostrongylus cantonensis , Animais , Anti-Helmínticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Ensaio de Imunoadsorção Enzimática , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Lactente , Imagem por Ressonância Magnética , Masculino , Meningoencefalite/tratamento farmacológico , Metilprednisolona/uso terapêutico , Infecções por Strongylida/tratamento farmacológico , Infecções por Strongylida/parasitologia
14.
Colloids Surf B Biointerfaces ; 183: 110446, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31465938

RESUMO

Cryptococcus neoformans-mediated meningoencephalitis is a critical infectious disorder of the human central nervous system. However, efficient treatment for the disease is limited due to the poor penetration across the blood brain barrier (BBB). Here, we develop a nose-to-brain drug delivery system utilizing nanostructured lipid carriers (NLCs). We demonstrated that fluorescent-dye-loaded NLCs efficiently uptake into the cytoplasm of encapsulated C. neoformans cells. In comparison with current antifungal drugs, the ketoconazole (keto)-NLCs show significantly increased antifungal activity against C. neoformans in vivo under various growth conditions. The NLCs show enhanced tissue colonization properties. Importantly, using animal imaging analyses, NLCs are able to enter brain tissues via the olfactory bulb region by intranasal administration, bypassing the BBB. In addition, NLCs maintain prolonged residence in tissues. In mouse brain tissue, keto-NLCs showed significantly enhanced antifungal activity when administered intranasally, drastically dampening the C. neoformans burden. Taken together, NLCs not only improve the ketoconazole penetration efficiency against capsulated C. neoformans cells, but also boost the efficacy of antifungal drugs. Most importantly, keto-NLCs significantly contribute to the treatment of cryptococcal meningoencephalitis in mice by bypassing the BBB via the olfactory system.


Assuntos
Criptococose/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Cetoconazol/administração & dosagem , Lipídeos/química , Meningoencefalite/tratamento farmacológico , Nanoestruturas/química , Administração Intranasal , Animais , Antifúngicos/administração & dosagem , Antifúngicos/química , Antifúngicos/farmacocinética , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/microbiologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/microbiologia , Criptococose/microbiologia , Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus neoformans/fisiologia , Portadores de Fármacos/química , Cetoconazol/química , Cetoconazol/farmacocinética , Meningoencefalite/microbiologia , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Transmissão , Nanoestruturas/ultraestrutura , Nariz/efeitos dos fármacos , Nariz/microbiologia , Tamanho da Partícula
15.
Pan Afr Med J ; 33: 2, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31303947

RESUMO

Ischemic stroke can result from multiple etiologies. It can also be a complication of tuberculous meningoencephalitis and determine its outcome. stroke secondary to tuberculous meningoencephalitis, occurs in 30% cases in the basal ganglia region, unusually in the thalamus. The mechanism of stroke in this condition is vasculitis. We report an unusual case of bilateral thalamic infarcts complicating tuberculous meningoencephalitis. Ischemic stroke in tuberculous meningoencephalitis is unpredictable with poor prognosis despite antituberculous drug treatment, emphasising the importance of primary prevention, particularly in tuberculosis endemic areas.


Assuntos
Infarto Encefálico/etiologia , Meningoencefalite/complicações , Acidente Vascular Cerebral/etiologia , Tuberculose Meníngea/complicações , Adolescente , Antituberculosos/administração & dosagem , Infarto Encefálico/diagnóstico , Humanos , Masculino , Meningoencefalite/tratamento farmacológico , Meningoencefalite/microbiologia , Prognóstico , Acidente Vascular Cerebral/diagnóstico , Tálamo/patologia , Tuberculose Meníngea/tratamento farmacológico
16.
Intern Med ; 58(23): 3469-3472, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31327825

RESUMO

An absence of skin lesions at the neurological onset may obscure the diagnosis of neuro-Sweet disease (NSD). We herein report a 32-year-old man with NSD in whom neurological symptoms preceded the development of skin lesions by 10 years. The patient exhibited four distinct neurological episodes: meningoencephalitis, scattered brain lesions, ocular flutter, and isolated seizures. Acute relapses responded to corticosteroid therapy, and the patient was successfully maintained on corticosteroid and dapsone combination therapy. NSD should be considered in the differential diagnosis of patients with recurrent neurological manifestations, especially with both meningeal and brain parenchymal involvement, even if no skin lesions are observed.


Assuntos
Doenças do Sistema Nervoso/etiologia , Síndrome de Sweet/diagnóstico , Administração Oral , Corticosteroides/administração & dosagem , Adulto , Anti-Infecciosos/administração & dosagem , Dapsona/administração & dosagem , Diagnóstico Diferencial , Diplopia/tratamento farmacológico , Diplopia/etiologia , Esquema de Medicação , Quimioterapia Combinada , Transtornos Neurológicos da Marcha/tratamento farmacológico , Transtornos Neurológicos da Marcha/etiologia , Humanos , Infusões Intravenosas , Masculino , Meningoencefalite/tratamento farmacológico , Meningoencefalite/etiologia , Metilprednisolona/administração & dosagem , Doenças do Sistema Nervoso/diagnóstico , Nistagmo Patológico/tratamento farmacológico , Nistagmo Patológico/etiologia , Prednisolona/administração & dosagem , Recidiva , Convulsões/tratamento farmacológico , Convulsões/etiologia , Dermatopatias/patologia , Síndrome de Sweet/complicações
17.
mBio ; 10(3)2019 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-31138748

RESUMO

Cryptococcus neoformans is an encapsulated yeast responsible for approximately a quarter of a million deaths worldwide annually despite therapy, and upwards of 11% of HIV/AIDS-related deaths, rivaling the impact of tuberculosis and malaria. However, the most effective antifungal agent, amphotericin B, requires intravenous delivery and has significant renal and hematopoietic toxicity, making it difficult to utilize, especially in resource-limited settings. The present studies describe a new nanoparticle crystal encapsulated formulation of amphotericin B known as encochleated amphotericin B (CAmB) that seeks to provide an oral formulation that is low in toxicity and cost. Using a 3-day delayed model of murine cryptococcal meningoencephalitis and a large inoculum of a highly virulent strain of serotype A C. neoformans, CAmB, in combination with flucytosine, was found to have efficacy equivalent to parental amphotericin B deoxycholate with flucytosine and superior to oral fluconazole without untoward toxicity. Transport of fluorescent CAmB particles to brain as well as significant brain levels of amphotericin drug was demonstrated in treated mice, and immunological profiles were similar to those of mice treated with conventional amphotericin B. Additional toxicity studies using a standardized rat model showed negligible toxicity after a 28-day treatment schedule. These studies thus offer the potential for an efficacious oral formulation of a known fungicidal drug against intrathecal cryptococcal disease.IMPORTANCE Cryptococcus neoformans is a significant global fungal pathogen that kills an estimated quarter of a million HIV-infected individuals yearly and has poor outcomes despite therapy. The most effective therapy, amphotericin B, is highly effective in killing the fungus but is available only in highly toxic, intravenous formulations that are unavailable in most of the developing world, where cryptococcal disease in most prevalent. For example, in Ethiopia, reliance on the orally available antifungal fluconazole results in high mortality, even when initiated as preemptive therapy at the time of HIV diagnosis. Thus, alternative agents could result in significant saving of lives. Toward this end, the present work describes the development of a new formulation of amphotericin B (CAmB) that encapsulates the drug as a crystal lipid nanoparticle that facilitates oral absorption and prevents toxicity. Successful oral absorption of the drug was demonstrated in a mouse model that, in combination with the antifungal flucytosine, provided efficacy equal to a parental preparation of amphotericin B plus flucytosine. These studies demonstrate the potential for CAmB in combination with flucytosine to provide an effective oral formulation of a well-known, potent fungicidal drug combination.


Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Criptococose/tratamento farmacológico , Meningoencefalite/tratamento farmacológico , Administração Oral , Anfotericina B/química , Animais , Antifúngicos/química , Cryptococcus neoformans/efeitos dos fármacos , Ácido Desoxicólico/uso terapêutico , Modelos Animais de Doenças , Combinação de Medicamentos , Composição de Medicamentos , Quimioterapia Combinada , Feminino , Flucitosina/uso terapêutico , Lipídeos/química , Masculino , Meningoencefalite/microbiologia , Camundongos , Nanopartículas/química , Ratos , Ratos Sprague-Dawley
18.
BMJ Case Rep ; 12(5)2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31142492

RESUMO

Cryptococcal meningitis is an opportunistic infection predominantly affecting immunocompromised patients but rarely can affect the immunocompetent. We describe a 53-year-old Caucasian man who presented complaining of a 2-week history of severe bilateral eye pain and diplopia. His only known risk factor was that he lived in a horse farm and recently shot bats and pigeons in his barn. He visited an outside hospital during this time without a diagnosis established. After further deliberation, we obtained a lumbar puncture (LP) which revealed an opening pressure (OP) of 27 cm H2O. Cerebrospinal fluid (CSF) and fungal cultures confirmed the presence of Cryptococcus neoformans The patient was diagnosed with C. neoformans-mediated meningoencephalitis and was initiated on the appropriate induction anti-fungal therapy. This case emphasises the need for clinicians to remain vigilant and consider cryptococcal meningitis in immunocompetent individuals even when classic symptoms of meningitis are absent.


Assuntos
Doenças dos Trabalhadores Agrícolas/diagnóstico , Imunocompetência/fisiologia , Meningite Criptocócica/diagnóstico , Meningoencefalite/diagnóstico , Doenças dos Trabalhadores Agrícolas/tratamento farmacológico , Doenças dos Trabalhadores Agrícolas/microbiologia , Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Cryptococcus neoformans , Diplopia/microbiologia , Quimioterapia Combinada , Dor Ocular/microbiologia , Fluconazol/administração & dosagem , Humanos , Masculino , Meningite Criptocócica/tratamento farmacológico , Meningoencefalite/tratamento farmacológico , Meningoencefalite/microbiologia , Pessoa de Meia-Idade , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/tratamento farmacológico , Doenças Raras
19.
Rinsho Shinkeigaku ; 59(4): 190-194, 2019 Apr 25.
Artigo em Japonês | MEDLINE | ID: mdl-30930365

RESUMO

The case was a 29-year-old male with no previous history of serious disease. He developed headache and fever, which then worsened and he was admitted to our hospital. His temperature was 38.3°C and he had a stiff neck. In cerebrospinal fluid (CSF) tests, the opening pressure was high, the cell count was increased, and the CSF/serum glucose ratio was decreased. In addition, he was positive for cryptococcal antigen. According to these findings, he was diagnosed with cryptococcal meningoencephalitis and antifungal treatment was initiated. His symptoms then improved, but on day 18 after admission, he developed convulsions, and on day 28, right visual field defects appeared. Brain MRI showed disseminated lesions in the bilateral cerebral cortex. Despite a decrease of the cryptococcal antigenic value in the CSF, the IgG index was elevated. IL-6, 8 and 10 in CSF were high levels on Day 1, then gradually reduced as the symptoms improved. But on Day 28, worsening of symptoms, IL-10 was significantly increased dispite IL-6 and 8 reducing. Therefore, the exacerbation of his symptoms and expansion of the lesions were not caused by the Cryptococcus itself, and it was considered that they were due to the late deterioration of cryptococcosis, which responded to steroid treatment.


Assuntos
Criptococose , Imunocompetência/imunologia , Meningoencefalite/imunologia , Meningoencefalite/microbiologia , Adulto , Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Antígenos de Fungos/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Cryptococcus neoformans/imunologia , Progressão da Doença , Humanos , Imunoglobulina G/líquido cefalorraquidiano , Imagem por Ressonância Magnética , Masculino , Meningoencefalite/diagnóstico , Meningoencefalite/tratamento farmacológico , Metilprednisolona/administração & dosagem , Neuroimagem , Pulsoterapia , Resultado do Tratamento , Voriconazol/administração & dosagem
20.
Vet J ; 244: 37-44, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30825893

RESUMO

Meningoencephalomyelitis of unknown origin (MUO) encompasses a group of idiopathic, most likely immune mediated, inflammatory central nervous system diseases that cause clinical, diagnostic and treatment challenges to veterinary neurologists. Clinical criteria for obtaining this presumptive diagnosis are currently available, and multiple treatment protocols have previously been investigated in small (prospective or retrospective) case series. As this group of diseases is considered fatal if left untreated, the identification of clinically usable prognostic indices could be of great value. This review provides an overview of recent developments in the clinical presentation, diagnostic findings, possible prognostic factors, treatment and outcome in dogs diagnosed with MUO.


Assuntos
Doenças do Cão/diagnóstico , Meningoencefalite/veterinária , Animais , Ciclosporina/uso terapêutico , Citarabina/uso terapêutico , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/tratamento farmacológico , Cães , Imunossupressores/uso terapêutico , Imagem por Ressonância Magnética/veterinária , Meningoencefalite/diagnóstico , Meningoencefalite/tratamento farmacológico , Prednisolona/uso terapêutico , Prognóstico , Resultado do Tratamento
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