Meningitis criptocócica asociada a hidrocefalia en un paciente inmunocompetente / Cryptococcal meningitis associated with hydrocephalus in an immunocompetent patient

La meningitis criptocócica es una infección infrecuente y con alta morbimortalidad, cuya presentación en pacientes inmunocompetentes es excepcional. Presentamos el caso de un varón de 67 años que ingresó por un cuadro subagudo de alteración de la marcha e incontinencia urinaria. El examen neurológico reveló incapacidad para mantenerse en pie y deterioro de la memoria. Las pruebas de imagen craneales mostraron hidrocefalia tetraventricular obstructiva con áreas de gliosis en los pedúnculos cerebelosos. Se realizó tratamiento endoscópico de la hidrocefalia, con toma de muestras de líquido cefalorraquídeo en las que se observó crecimiento de Cryptococcus neoformans. El paciente mejoró con el tratamiento endoscópico y tras completar la terapia antifúngica intravenosa con anfotericina B liposomal y fluconazol durante diez semanas. La meningitis criptocócica en pacientes inmunocompetentes se trata con antifúngicos. En raras ocasiones se presenta con hidrocefalia, situación que requiere tratamiento quirúrgico mediante derivaciones del líquido cefalorraquídeo o técnicas endoscópicas. (AU)

Cryptococcal meningitis is an infrequent infection with high morbidity and mortality. Its presentation in immuno-competent patients is rare.We present the case of a 67-year-old male who was admitted for subacute symptoms of gait disturbance and urinary incontinence. Neurological examination revealed inability to stand and memory impairment. Cranial im-aging showed obstructive tetraventricular hydrocephalus with areas of gliosis in the cerebellar peduncles. Endo-scopic treatment of hydrocephalus was performed and cerebrospinal fluid samples taken revealing the growth of Cryptococcus neoformans. The patient improved with the endoscopic treatment and after completing intravenous antifungal therapy with liposomal amphotericin B and flu-conazole for ten weeks.Antifungals are used to treat cryptococcal meningitis in immunocompetent patients. On rare occasions, it presents with hydrocephalus, a situation that requires surgical treat-ment using cerebrospinal fluid diversions or endoscopic techniques. (AU)

Post-infectious inflammatory response syndrome in an HIV-negative patient after Cryptococcus gattii meningoencephalitis: a case report and review of the literature.

BACKGROUND: Cryptococcal meningitis (CM) is an inflammatory mycosis of the central nervous system caused by meninge infection or brain parenchyma with Cryptococcus species. It is associated with high morbidity and mortality, and patients with acquired immune deficiency syndrome are particularly susceptible. There have been increasing reports of CM in HIV-negative patients in China over the last few years. CASE PRESENTATION: A 31-year-old healthy Chinese male presented with fever and gradually developed headache, projectile vomiting, and other manifestations that were later confirmed as Cryptococcus gattii meningoencephalitis. However, multiple disease changes occurred during the course of treatment, and the regimen was accordingly modified after the diagnosis of post-infectious inflammatory response syndrome (PIIRS). The patient eventually recovered. CONCLUSION: There has been a growing trend in the incidence of C. gattii meningoencephalitis in HIV-negative patients. It shows rapid onset and severe prognosis. This case report can provide a reference to treat PIIRS following CM in HIV-negative patients.

Cryptococcal Meningitis and Post-Infectious Inflammatory Response Syndrome in a Patient With X-Linked Hyper IgM Syndrome: A Case Report and Review of the Literature.

The hyper IgM syndromes are a rare group of primary immunodeficiency. The X-linked Hyper IgM syndrome (HIGM), due to a gene defect in CD40L, is the commonest variant; it is characterized by an increased susceptibility to a narrow spectrum of opportunistic infection. A few cases of HIGM patients with Cryptococcal meningoencephalitis (CM) have been described in the literature. Herein we report the case of a young male diagnosed in infancy with HIGM who developed CM complicated by a post-infectious inflammatory response syndrome (PIIRS), despite regular immunoglobulin replacement therapy and appropriate antimicrobial prophylaxis. The patient was admitted because of a headache and CM was diagnosed through detection of Cryptococcus neoformans in the cerebrospinal fluid. Despite the antifungal therapy resulting to negative CSF culture, the patient exhibited persistent headaches and developed diplopia. An analysis of inflammatory cytokines on CSF, as well as the brain MRI, suggested a diagnosis of PIIRS. Therefore, a prolonged corticosteroids therapy was started obtaining a complete resolution of symptoms without any relapse.

Cryptococcal meningitis presented as sudden hearing loss: A case study.

BACKGROUND: This case report emphasizes that cryptococcal meningitis could be uncommonly presented to otolaryngologists as sudden onset of hearing loss, especially in patients with underlying diseases that could cause immunocompromise, and highlights the importance of differentiated diagnosis on sudden hearing loss before steroid therapy. It also demonstrates that prompt and sufficient fungicidal therapy with appropriate supportive treatment is crucial for a good prognosis on cryptococcal meningitis. CASE PRESENTATION: A diabetic adult with untreated chronic hepatitis B was admitted complaining of sudden onset of left-sided hearing loss, following unexpected aggravating headache with meningeal signs after hospitalization with days of intratympanic steroid therapy. Cryptococcal meningitis was confirmed through lumbar puncture showing positive India ink staining and microbial culture of the cerebrospinal fluid (CSF). Fortunately, the patient recovered after prompt and adequate fungicidal therapy plus appropriate supportive treatment at last, though persistent hearing loss remained. CONCLUSIONS: Cryptococcal meningitis could be presented in a very concealed way as sudden hearing loss, especially in patients with underlying diseases that could cause immunosuppression. Differentiated diagnosis on sudden hearing loss before steroid therapy is important.

Surgical treatment and operation time in human immunodeficiency virus-negative cryptococcal meningitis.

There are still no unified guidelines of surgical treatment and timing for human immunodeficiency virus (HIV)-negative patients with cryptococcal meningitis (CM).The clinical data and follow-up data were collected from HIV-negative CM patients in Xiangya Hospital of Central South University from January 2009 to November 2018, and 42 patients who were treated with surgical intervention were enrolled in the present study. These 42 patients were divided into ventriculoatrial (VA) group, ventriculoperitoneal group, external ventricle drainage (EVD) group, hydrocephalus (HYC) group, non-HYC group, EVD group, and non-EVD group (VA/ ventriculoperitoneal) according to different surgical procedures. Statistical analyses were conducted using SPSS (version 19.0, Chicago, IL).Signs of headache, fever, and loss of consciousness in the VA group were significantly improved compared with the EVD group at 1 week after operation (P < .05). The mortality rate of the VA group was significantly lower than that of the EVD group (P < .05). Moreover, male patients were more prone to have HYC (P < .05). Younger patients tended to develop HYC (P < .05). Cerebrospinal fluid sugar in the non-HYC group was significantly lower compared with the HYC group (P < .05). Time of CM-to-operation in the non-HYC group was markedly shorter compared with the HYC group (P < .01).VA procedure could be one of the first choices for the treatment of uncontrollable intracranial hypertension caused by CM. Severe uncontrollable headache, loss of consciousness, and cerebral hernia were indications of emergency surgery. Repeated headache, hearing impairment, and especially progressive loss of vision were indications of early surgery to avoid permanent damage to nerve functions of HIV-negative CM patients.

Impaired consciousness and decreased glucose concentration of CSF as prognostic factors in immunocompetent patients with cryptococcal meningitis.

BACKGROUND: Cryptococcal meningitis (CM) is the most common fungal infection of the central nervous system and has high morbidity and mortality. Almost studies about prognostic factors have largely focused on the immunocompromised population rather than immunocompetent patients. So that we sought to conduct a retrospective study to determine prognostic factors which predict the outcomes in immunocompetent patients with CM. METHODS: We retrospectively collected and analyzed the demographic and clinical data of 76 apparently immunocompetent patients with cryptococcal meningitis from January 2003 to June 2019 in China. The clinical outcome was graded by the Glasgow outcome scale (GOS) at discharge, and patients were divided into good (score of 5) and unfavorable (score of 1-4) outcome groups, potential prognostic factors were analyzed. RESULTS: Non-parametric test confirmed that unfavorable outcome was associated with lower glucose level of CSF(P = 0.001), and Pearson's χ2 analysis confirmed that unfavorable outcome was associated with opening pressure of CSF(>300mmH20, P = 0.038), impaired consciousness (P = 0.001), hydrocephalus(P = 0.045), and Shunt surgery (P = 0.045), and then multiple logistic regression analysis confirmed that impaired consciousness(P = 0.015) and lower glucose concentration of CSF(P = 0.012) increased the likelihood of unfavorable outcome in CM patients. CONCLUSION: Impaired consciousness and decreased glucose concentration of CSF were independently prognostic factors which predict the unsatisfactory outcome in immunocompetent patients with CM.

Successful treatment with corticosteroids for refractory deterioration of cryptococcal meningitis with an increasing cryptococcal antigen titer.

We report a 55-year-old man with Cryptococcus neoformans meningitis who showed refractory deterioration twice with an increased cerebrospinal fluid cryptococcal antigen titer during the course of treatment. Although the initial deterioration was temporarily improved by placement of a ventriculoperitoneal shunt, he experienced deterioration again. However, he improved after administration of systemic corticosteroids. The present case suggests that systemic corticosteroid can be a choice of treatment to rescue immunocompetent patients with Cryptococcus neoformans meningitis and severe deterioration, even if cerebrospinal fluid analysis shows an increased cryptococcal antigen titer.

Unusual Presentation of Severe Endobronchial Obstruction Caused by Cryptococcus gattii in a Child.

Disease caused by Cryptococcus gattii typically manifests as meningoencephalitis or pulmonary nodules. Endobronchial lesions are rare, and most cases are caused by Cryptococcus neoformans. We describe here a case of endobronchial disease in a child caused by C gattii. The disease spectrum in this patient was notable for the discovery of anti-granulocyte macrophage colony-stimulating factor autoantibodies.

The significance of anti-granulocyte-macrophage colony-stimulating factor antibodies in cryptococcal infection: case series and review of antibody testing.

We report two cases of cryptococcosis, associated with anti-granulocyte-macrophage colony-stimulating factor antibodies. We review this recently identified acquired form of autoimmune immune deficiency and discuss the potential applications of granulocyte-macrophage colony-stimulating factor antibody testing by enzyme-linked immunosorbent assay.

FATAL cryptococcal meningitis in a child with hyper-immunoglobulin M syndrome, with an emphasis on the agent.

Following a fatal case of Cryptococcus neoformans meningitis in a child with X-linked hyper-immunoglobulin M syndrome (XHIGM), we evaluated the fungal isolate in an experimental infection in a mouse model with respect to microbiology, epidemiology, virulence and response to therapy. The minimum inhibitory concentrations for antifungals in the susceptibility test were 0.5mg/L for amphotericin B, 4.0mg/L for fluconazole and 0.12mg/L for voriconazole. Evaluation of pathogenicity by means of an experimental infection in BALB/c mice showed that fungus isolated from the blood and cerebrospinal fluid of the child was able to disseminate, reaching the spleen, lungs and brain, where it caused significant macroscopic alterations in the size and texture of each organ. Treatment of infected mice with amphotericin B reduced the fungal load in the spleen and lungs, but not in the brain.

Cryptococcal Meningitis Presenting as New-Onset Seizures in an Immunocompetent Patient.

This report describes a 30-year-old immunocompetent male with new-onset seizures, later found on imaging to have 2 enhancing lesions in the brain. The patient underwent a left parietal craniectomy with resection of one of the masses, which demonstrated focal areas of necrosis and many small cystic structures positive for periodic acid-Schiff and Gomori's methenamine silver special stain. Numerous laboratory examinations, including HIV test, rapid plasma reagin, toxoplasma immunoglobulin G and immunoglobulin M, Lyme, cytomegalovirus, tuberculosis, cysticercosis, and Echinococcus serology, were all negative. Despite negative cerebrospinal fluid (CSF) culture and several negative CSF antigen tests, continued investigation, and follow-up, CSF antigen testing ultimately revealed Cryptococcus as the causative agent. In light of the mysterious and unusual presentation, the authors discuss potential infectious differential diagnoses in patients with atypical clinical presentation, laboratory tests, and surgical pathology.

The clinical characteristics and therapeutic outcomes of cryptococcal meningitis in elderly patients: a hospital-based study.

BACKGROUND: The elderly, and especially those with an immuno-compromised status, are vulnerable to infectious diseases. The purpose of this study was to examine the clinical characteristics and therapeutic outcomes of cryptococcal meningitis (CM) in elderly patients in Taiwan. METHODS: Ninety-nine adult patients with CM were identified during a 15-year study period (2002-2016), of whom 38 elderly (≥ 65 years) patients (16 men and 22 women, median age 72.9 years; range 65-86 years) were included for analysis. The clinical characteristics and therapeutic outcomes of these patients were analyzed and compared to non-elderly adult patients (< 65 years) with CM. RESULTS: Among the 38 patients, diabetes mellitus was the most common underlying condition (15), followed by adrenal insufficiency (7), malignancy (6), hematologic disorders (5), chronic obstructive pulmonary disease (5), autoimmune diseases (3), liver cirrhosis (3) and acquired immunodeficiency syndrome (1). Altered consciousness (29), fever (21) and headache (17) were the leading clinical manifestations. Positive cerebrospinal fluid and blood cultures for Cryptococcus (C.) neoformans were found in 26 and 9 patients, respectively. There were significant differences in gender, altered consciousness and recent cerebral infarction between the elderly and non-elderly groups. The elderly group had a high mortality rate (36.8%, 14/38), and the presence of cryptococcemia was the most significant prognostic factor. CONCLUSIONS: This study offers a preliminary view of the clinical characteristics of CM in the elderly. The results suggest that elderly patients (≥ 65 years) are more vulnerable to CM than adults aged < 65 years. Compared to the non-elderly group, the elderly group had female predominance, higher rates of altered consciousness and recent cerebral infarction as the clinical presentation. The presence of cryptococcemia was a significant prognostic factor in the elderly group. This study is limited by the small number of patients, and further large-scale studies are needed to better delineate this specific infectious syndrome.

Lacunar Stroke in Cryptococcal Meningitis: Clinical and Radiographic Features.

OBJECTIVE: Cryptococcal meningitis carries a high mortality, and survivors are left with considerable neurologic sequelae and marked disability. We lack a clear understanding of the pathogenesis of neurologic sequelae and description of stroke features in this population. We aim to describe clinical and radiographic features and predictors of stroke in a cohort of patients with cryptococcal meningitis. METHODS: We collected key information on patients diagnosed with cryptococcal meningitis at the University of Colorado Hospital between 2000 and 2018 (n = 42). Of those, 32 had neuroimaging studies available. Bivariate and risk ratio estimates regression models were performed to identify predictors of stroke. RESULTS: We found a 26% ischemic stroke complication rate in individuals with cryptococcal meningitis. Most strokes were acute (75%), lacunar (100%), multiple (88%), bilateral (63%), and involving the basal ganglia (75%). Presence of malignancy (38% versus 8%, P = .085) was higher in stroke in individuals with cryptococcal meningitis, although not statistically significant. Every unit decrease in hemoglobin and serum sodium were predictors for 1.35 and 1.14 times increase in the risk of ischemic stroke, respectively. The presence of hyponatremia carried a RR of 5.7 (95% confidence interval, 1.7-34, P = .005). Cryptococcal meningitis lead to death in 19% of patients and a considerable rate of neurologic sequela among survivors. CONCLUSIONS: Cryptococcal meningitis carries a high risk of lacunar stroke, particularly in the basal ganglia. Cryptococcal meningitis-associated stroke is common and frequently associated with neurologic disability among survivors. We need to understand the possible role of malignancy, anemia, and hyponatremia in the onset of ischemic stroke.

Comparison and Correlation of Magnetic Resonance Imaging and Clinical Severity in Nonhuman Immunodeficiency Virus Patients with Cryptococcal Infection of Central Nervous System.

BACKGROUND: The incidence of cryptococcal meningitis among immunocompetent patients increases, especially in China and imaging plays an important role. The current study was to find the correlation between magnetic resonance imaging (MRI) manifestation and clinical severity in nonhuman immunodeficiency virus patients with cryptococcal infection of central nervous system (CNS). METHODS: A total of 65 patients with CNS cryptococcal infection from August 2014 to October 2016 were retrospectively included in this study. All the patients had MRI data and clinical data. The patients were divided into two groups according to whether the patients were confirmed with identifiable underlying disease. Comparison and correlation of MRI and clinical data in both groups were investigated using independent sample t- test, Chi-square test, Mann-Whitney test and Spearman rank correlation analysis. RESULTS: In all 65 patients, 41 cases (41/65, 63.1%; Group 1) had normal immunity and 24 cases (24/65, 36.9%; Group 2) had at least one identifiable underlying disease. Fever, higher percentage of neutrophil (NEUT) in white blood cell (WBC), and increased cell number of cerebral spinal fluid (CSF) were much common in patients with underlying disease (Group 1 vs. Group 2: Fever: 21/41 vs. 21/24, χ2 = 8.715, P = 0.003; NEUT in WBC: 73.15% vs. 79.60%, Z = -2.370, P = 0.018; cell number of CSF: 19 vs. 200, Z = -4.298, P < 0.001; respectively). Compared to the patients with normal immunity, the lesions are more common in the basal ganglia among patients with identifiable underlying disease (Group 1 vs. Group 2: 20/41 vs. 20/24, χ2 = 7.636, P = 0.006). The number of the involved brain areas in patients with identifiable underlying disease were well correlated with the number of cells and pressure of CSF (r = -0.472, P = 0.031; r = 0.779, P = 0.039; respectively). CONCLUSIONS: With the increased number of the involved brain areas in patients with identifiable underlying disease, the body has lower immunity against the organism which might result in higher intracranial pressure and more severe clinical status.

Criptococosis cerebral, voriconazol, niveles plasmáticos y síndrome de reconstitución inmune: reporte de un caso / Cerebral cryptococcosis and immune reconstitution inflammatory syndrome: case report

We report a 45-year-old male with AIDS who had a Cryptococcus neoformans central nervous system infection. He was treated with amphotericin B deoxycholate subsequently changed to voriconazole due to systemic toxicity of the former. Plasma levels of voriconazole were insufficient with a standard dose (0.7 μg/mL), therefore, the dose was increased thereafter to reach appropriate levels (4.5 μg/mL). Anti-retroviral therapy was started five weeks after voriconazole initiation with non-interacting drugs and he was discharged after a favorable evolution. He was re-admitted three months later due to seizures; a brain magnetic resonance showed new sub-cortical nodules. After excluding alternative causes and demonstrating fungal eradication, an immune reconstitution inflammatory syndrome (IRIS) event was suspected and treated with a short course of steroids. His evolution was satisfactory.

Cryptococcal meningitis mimicking cerebral infarction: a case report.

Cryptococcal meningitis (CM) is the most common type of fungal meningitis. The clinical symptoms of CM are nonspecific, and neuroimaging characteristics are variable. Herein, we present a case of a senile female with CM that was once misdiagnosed as cerebral infarction. Her condition worsened and she developed hydrocephalus. No apparent predisposing factors of CM were reported in this patient. The diagnosis of CM was definitely made after India ink staining of cerebrospinal fluid was positive. This case indicates that clinicians should bear cryptococcal infection in mind when the symptoms are nonspecific and neuroimaging findings are atypical.

Cryptococcus gattii Complex Infections in HIV-Infected Patients, Southeastern United States.

Cryptococcus gattii traditionally infects immunocompetent hosts and causes devastating pulmonary or central nervous system disease. However, this infection rarely occurs in patients infected with HIV. We report 3 cases of HIV-associated C. gattii complex infections in the southeastern United States. Detection of C. gattii in HIV-infected patients in this region warrants increased awareness of this threat to ensure appropriate diagnosis and treatment to optimize patient outcomes.