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Background: Cryptococcosis is an invasive fungal infection primarily affecting lungs and potentially spreading to the central nervous. This fungal infection might be misdiagnosed as other infection diseases, such as tuberculosis; granulomatous diseases, like sarcoidosis; and even neoplastic diseases. Some previous reports described cases of cryptococcomas resembling brain tumors. In this paper, we present a very rare presentation of brain cryptococcoma mimicking a malignant glioma. To the best of our knowledge, this is the third case description in the literature. Case Description: A 64-year-old male patient presented at the hospital with a history of progressive frontal headache for 1 month, becoming moderate to severe, associated with visual changes, without nausea or vomiting. No fever was reported. He was a heavy smoker and denied other relevant previous medical data. Neuroimage disclosed a right temporal expansive lesion initially considered a malignant glioma. The patient underwent a right temporal craniotomy and biopsy revealed a cryptococcoma. Conclusion: Cryptococcomas characteristics in magnetic resonance are quite nonspecific. They should always be included in differential diagnosis of expansive brain lesions, both malignant and benign. Therefore, once cryptococcomas may resemble like other intracranial expansive lesions, biopsy should always be carried out to clarify diagnosis and avoid inadequate treatment and definition of prognosis only based on radiological patterns.
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Neurocryptococcosis, a meningoencephalitis caused by Cryptococcus spp, is treated with amphotericin B (AmB) combined with fluconazole. The integrity of the brain-blood barrier and the composition of the cerebrospinal fluid (CSF) may change due to infectious and/or inflammatory diseases such as neurocryptococcosis allowing for the penetration of AmB into the central nervous system. The present study aimed to develop LC-MS/MS methods capable of quantifying AmB in CSF at any given time of the treatment in addition to plasma, plasma ultrafiltrate, with sensitivity compatible with the low concentrations of AmB reported in the CSF. The methods were successfully validated in the four matrices (25 µl, 5-1,000 ng ml-1 for plasma or urine; 100 µl, 0.625-250 ng ml-1 for plasma ultrafiltrate; 100 µl, 0.1-250 ng ml-1 for CSF) using protein precipitation. The methods were applied to investigate the pharmacokinetics of AmB following infusions of 100 mg every 24 h for 16 days administered as a lipid complex throughout the treatment of a neurocryptococcosis male patient. The methods allowed for a detailed description of the pharmacokinetic parameters in the assessed patient in the beginning (4th day) and end of the treatment with AmB (16th day), with total clearances of 7.21 and 4.25 L h-1, hepatic clearances of 7.15 and 4.22 L h-1, volumes of distribution of 302.94 and 206.89 L, and unbound fractions in plasma ranging from 2.26 to 3.25%. AmB was quantified in two CSF samples collected throughout the treatment with concentrations of 12.26 and 18.45 ng ml-1 on the 8th and 15th days of the treatment, respectively. The total concentration of AmB in plasma was 31 and 20 times higher than in CSF. The unbound concentration in plasma accounted for 77 and 44% of the respective concentrations in CSF. In conclusion, the present study described the most complete and sensitive method for AmB analysis in plasma, plasma ultrafiltrate, urine, and CSF applied to a clinical pharmacokinetic study following the administration of the drug as a lipid complex in one patient with neurocryptococcosis. The method can be applied to investigate the pharmacokinetics of AmB in CSF at any given time of the treatment.
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The following case is of a 59-year-old man, undergoing no medication, with no pathological history or others risk factors, who presented dizziness, fever and asthenia twenty days before admission. The patient was admitted for investigation when the asthenia intensified, followed by seizures. On admission, blood count, biochemical tests and chest computed tomography were normal, a serological test for anti-HIV proved negative, while the magnetic resonance of the brain showed signs suggestive of meningoencephalitis. Cerebrospinal fluid (CSF) analysis suggested bacterial meningitis due to increased leukocytes with a predominance of polymorphonuclear cells, reduced glucose and increased proteins as well as positive Gram cocci in pairs by Gram and negative fungi by India ink test. Treatment with ceftriaxone was started. Since there was no significant improvement, CSF analysis was repeated on the seventh day of treatment. Intracranial pressure was measured by manometry (29 mmHg) and CSF analysis showed the presence of encapsulated yeasts similar to Cryptococcus neoformans by the India ink test. The treatment was modified to liposomal amphotericin B and flucytosine; the intracranial hypertension was controlled by repeated CSF punctures. After fourteen days of antifungal treatment, the patient presented visual turbidity and bilateral papillar edema, so corticosteroid therapy was prescribed. The evolution was favorable, with progressive resolution of symptoms, improvement of CSF parameters and visual acuity. The patient was discharged eight weeks after admission, with outpatient guidance. Corticosteroid therapy associated with antifungal therapy proved to be beneficial in this case, since following the introduction of corticosteroids there was progressive visual improvement.
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Humanos , Acuidade Visual , Neurite Óptica , Meningites Bacterianas , Corticosteroides , Cryptococcus gattiiRESUMO
The meningococcal disease manifestation associated with the presence of Cryptococcus neoformans is rare. There are no reports in the literature about these simultaneous infections in immunocompetent patients. The aim of the present study is to describe the first case of fulminant septic shock by Neisseira meningitidis associated with Cryptococcus neoformans coinfection in an immunocompetent patient. We describe a case of an immunocompetent 74-year-old Caucasian woman who presented with fulminant acute meningococcemia associated with cryptococcal meningitis, which progressed to worsening general condition and died of septic shock and multiple organ dysfunctions in less than 48 hours. This case report demonstrates the possibility of coinfections related to Neisseria meningitidis and Cryptococcus neoformans, even in immunocompetent patients, which represent a diagnostic challenge for clinicians, thus encouraging further studies for a better understanding.
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Cryptococcosis is a life-threatening mycosis reported mainly in human adults with low frequency in children. High mortality rates may occur in cases with late diagnosis therefore, a timely suspicion of this pathology is important. Cryptococcus gattii is the less prevalent species complex predominantly isolated from apparently normal hosts. We report a fatal case of neurocryptococcosis in a Colombian minor without known risk factors, in Barranquilla, Colombia. The patient was hospitalized for neurological assessment with a recent history of intense headache, vomiting, anorexia, loss of consciousness, drowsiness, inability to recognize family members, disorientation, aphasia and anxiety. Despite initiating antifungal treatment after isolation of the fungus from cerebrospinal fluid (CSF), the patient died early due to his deteriorated condition.
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Líquido Cefalorraquidiano/microbiologia , Criptococose/etiologia , Antifúngicos/uso terapêutico , Criança , Colômbia , Criptococose/tratamento farmacológico , Criptococose/microbiologia , Cryptococcus gattii/isolamento & purificação , Cryptococcus gattii/patogenicidade , Humanos , MasculinoRESUMO
A criptococose é uma micose sistêmica, de ocorrência relativamente rara, potencialmente grave, geralmente oportunista e de elevada frequência em pacientes imunossuprimidos, com amplo espectro de acometimento de órgãos, tropismo especial para o sistema nervoso central (SNC), evolução subaguda ou crônica, e manifestações clínicas variadas. Este estudo descritivo, retrospectivo, observacional, transversal, objetivou descrever os dados demográficos, clínicos, comorbidades, sintomas ou sinais, e o prognóstico de pacientes com neurocriptococose, atendidos e internados no Hospital das Clínicas (HC) da Universidade Federal de Minas Gerais desde 2000 até 2013. O HC é unidade universitária, pública e geral, de nível terciário e quaternário, com 450 leitos de internação, integrado ao Sistema Único de Saúde (SUS), com clientela universalizada, cerca de 40% do total proveniente do interior do estado de Minas Gerais, predominando da região Metropolitana de Belo Horizonte, aberto à transferência de pacientes de todo o território mineiro, com área de abrangência de população de mais de cinco milhões de pessoas, de todas as faixas etárias e todas as especialidades médicas, encaminhados pela intensidade de sua expressão clínica, especialmente em situação crítica, o que torna sua casuísticade máxima gravidade. Os pacientes foram internados a partir do Pronto Socorro do HC que admite, em média, 80 pacientes com urgência clínicas por dia, incluindo obstétricas, e excluídas aquelas devido à acidente ou violência de qualquer natureza. Foram analisados 40 pacientes com neurocriptococose o que significou 0,13% de toda demanda de admissão de urgência para o período estudado, cerca de 603.000 pessoas, isto é 12% da população referida, e associou-se à letalidade de 25%; com frequência da distribuição de acordo com o gênero em 2:1, entre homens e mulheres, respectivamente; e nas faixas etárias entre 20-40, 40-60 e mais de 60 anos de idade, de 36%, 42%, e 22%, respectivamente, sendo a proporção entre 20 a 60 e mais de 60 de aproximadamente, 2:1. A neurocriptococose associou-se em mais de 50% dos pacientes com a: SIDA (57,5%); internação prévia (52,5%) relacionada à quimio e corticoterapia, transplante, cirurgias para ressecção de neoplasias; e, em menos de 20% com doença cardiovascular hipertensiva sistêmica (17,5%), cirurgia prévia (15%) e tuberculose (5%). A sintomatologia isolada presente em pelo menos 40% dos pacientes foi: cefaleia (70%), astenia (50%), febre (45%), vômitos (40%); entretanto, em até um terço deles constituiu-se de: emagrecimento (30%), tontura (30%), dor abdominal (27,5%), convulsão (22,5%). As anormalidades mais e menos especificamente indicadoras de acometimento do SNC foram cefaleia; e, vômito, tontura e convulsão,respectivamente. As alterações do exame neurológico foram relacionadas aos distúrbios da consciência (35%), lesão focal (30%), alteração da marcha (25%) e distúrbio do comportamento (15%). A concomitância de cefaléia, convulsão e vômitos foi anotada em 5% dos pacientes; enquanto de cefaléia e convulsão em 22,5%. Foi observada, à admissão hospitalar, em 40%, dos pacientes a associação de cefaléia e vômito; mas todos os pacientes com vômito e também os com lesão focal apresentavam cefaleia. A presença de cefaleia não foi descrita em 35% dos pacientes com alteração da consciência à admissão hospitalar. O diagnóstico presuntivo de neurocriptococose deve ser realizado, independentemente da sintomatologia clínica neurológica, o que realça a percepção geral do paciente, incluindo epidemiologia, história familiar, história prévia, manifestações clínicas, presença de imunossupressão, para surpreender a criptococose, e iniciar a terapêutica o mais apidamente possível para que possa ser reduzida sua letalidade. A limitação deste estudo relaciona-se ao fato de ter sido retrospectivo, em que o controle dos dados registrados é muito limitada, sendo impossível corrigir a ausência de dados registrados. (AU)
Cryptococcosis is a systemic, relatively rare, potentially severe, often opportunistic and systemic mycosis in immunosuppressed patients with a broad spectrum of organ involvement, a special central nervous system (CNS) tropism, subacute or chronic clinical manifestations. This descriptive, retrospective, observational, cross-sectional study aimed to describe the demographic, clinical, comorbidities, symptoms or signs, and the prognosis of patients with neurocryptococcosis, attended and hospitalized at the Hospital das Clínicas (HC) of the Universidade Federal de Minas Gerais since 2000 until 2013. The HC is a university unit, public and general, tertiary and quaternary level, with 450 beds of hospitalization, integrated into the Unified Health System (SUS), with a universalized clientele, about 40% of the total coming from the interior of the state of Minas Gerais, predominating in the metropolitan region of Belo Horizonte, which is open to the transfer of patients from all over Minas Gerais, with an area of population of more than five million people, of all age groups and all medical specialties. intensity of its clinical expression, especially in a critical situation, which makes its series of age.The patients were hospitalized from the HC Emergency Room, which admitted, on average, 80 urgently needed clinics per day, including obstetrics, and excluded due to accidents or violence of any kind. We analyzed 40 patients with neurocryptococcosis, which represented 0.13% of all urgent admission demands for the period studied, about 603,000 people, ie 12% of the referred population, and was associated with a 25% lethality; with frequency of distribution according to gender in 2: 1, between men and women, respectively; and in the age groups between 20-40, 40-60 and over 60 years of age, of 36%, 42%, and 22% respectively, the ratio being between 20 to 60 and more than 60 of approximately 2: 1. Neurocryptococcosis was associated in more than 50% of patients with: AIDS (57.5%); previous hospitalization (52.5%) related to chemo and corticoid therapy, transplantation, surgeries for resection of neoplasias; and in less than 20% with systemic hypertensive cardiovascular disease (17.5%), previous surgery (15%) and tuberculosis (5%). The isolated symptoms present in at least 40% of the patients were: headache (70%), asthenia (50%), fever (45%), vomiting (40%); (30%), dizziness (30%), abdominal pain (27.5%), and seizure (22.5%). The most and least specific abnormalities of CNS involvement were headache; and, vomiting, dizziness and convulsion, respectively. Changes in neurological examination were related to disturbances of consciousness (35%), focal lesion (30%), gait alteration (25%) and behavior disorder (15%). The concomitance of headache, convulsion and vomiting was noted in 5% of the patients; while headache and seizure in 22.5%. The association of headache and vomiting was observed in 40% of patients; but all patients with vomiting and those with focal lesion also had headache. The presence of headache was not described in 35% of patients with altered consciousness at hospital admission. The presumptive diagnosis of neurocryptococcosis should be performed independently of the clinical neurological symptomatology, which highlights the general perception of the patient, including epidemiology, family history, previous history, clinical manifestations, presence of immunosuppression, to start cryptococcosis, and initiate therapy. as soon as possible so that their lethality can be reduced. The limitation of this study is the fact that it was retrospective, in which the control of the recorded data is very limited, and it is impossible to correct the absence of recorded data. (AU)
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Humanos , Masculino , Feminino , Criptococose , Sistema Único de Saúde , Humanos , Infecções Fúngicas do Sistema Nervoso Central , MicosesRESUMO
Cryptococcus gattii, a species belonging to the Cryptococcus complex which occurs endemically in tropical and subtropical regions, has been reported as a causative agent of cryptococcosis in healthy individuals. We report a case of meningitis in HIV-negative patient from Cuiaba, MT, in the Midwestern region of Brazil. Cryptococcus gattii AFLP6/VGII was isolated from cerebrospinal fluid and molecular typing was performed by URA5-RFLP. The in vitro susceptibility profile was determined using the standard method according to the document M27A3, CLSI 2008. C. gattii AFLP6/VGII was shown to be susceptible to the antifungals tested. Treatment with 0.8 mg/kg of amphotericin B was initiated; however, the patient died 2 days after the onset of therapy.