Central Nervous System Histoplasmosis Research Articles

Central Nervous System Histoplasmosis: An Updated Insight.

Histoplasmosis is one of the systemic mycoses that can involve the Central Nervous System (CNS), and it is caused by the dimorphic ascomycete species of the Histoplasma capsulatum complex. Once in the CNS, this pathogen causes life-threatening injuries that are associated with clinical manifestations of meningitis, focal lesions (abscesses, histoplasmomas), and spinal cord injuries. The present review provides updated data and highlights a particular vision regarding this mycosis and its causative agent, as well as its epidemiology, clinical forms, pathogenesis, diagnosis, and therapy, focusing on the CNS.

Reactivation of Disseminated Histoplasmosis With Central Nervous System Involvement Following a Primary Gastrointestinal Histoplasmosis Infection: A Case Report

A 78-year-old white male with chronic pancytopenia presented with acute transient aphasia and dysarthria. He had a National Institutes of Health Stroke Scale (NIHSS) of zero. Physical examination revealed slight aphasia with mild dysarthria. Brain magnetic resonance imaging (MRI) revealed nine ring-enhancing lesions in the left precentral gyrus with significant vasogenic edema. Lung computed tomography (CT) showed no evidence of pulmonary nodules. The serology of blood and urine for infectious organisms was negative. Four weeks later, the patient was re-admitted with worsening dysarthria and right upper extremity weakness. Repeat head MRI showed a slight increase in the size of the multiple supratentorial ring-enhancing lesions. The magnetic resonance spectroscopy (MRS) findings of the evaluated lesion suggested a fungal etiology. Empiric amphotericin B treatment was initiated, which mitigated central nervous system (CNS) ring-enhancing lesions and resolved the patient’s neurological deficits. Early empiric medical treatment of CNS histoplasmosis should be considered in the setting of multiple CNS ring-enhancing lesions and a positive history of histoplasmosis infection, despite negative serological studies.

VP Shunt With Recurrent Malfunction in Two Pediatric Patients: Is the Hydrocephalus Truly Idiopathic?

VP Shunt With Recurrent Malfunction in Two Pediatric Patients: Is the Hydrocephalus Truly Idiopathic?

Histoplasmosis of the Central Nervous System: A Case Series between 1990 and 2019 in French Guiana

.Disseminated histoplasmosis is the most frequent acquired immunodeficiency syndrome–defining illness in French Guiana. Paradoxically, central nervous system (CNS) involvement has been scarcely described. We aimed to identify CNS histoplasmosis in our territory. We conducted an observational, multicentric, descriptive, and retrospective study including patients with proven or probable CNS histoplasmosis according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MGS). The study population consisted of patients admitted in one of the hospitals of French Guiana between January 1, 1990 and December 31, 2019. During the study period, 390 cases of HIV-associated histoplasmosis were recorded, in which six of them had CNS infections with Histoplasma capsulatum. The male to female sex ratio was 0.25, and the median age at diagnosis was 37.5 years. The median CD4 count was 42 cells/mm3 ([IQR: 29–60]). All patients had disseminated histoplasmosis. Usual signs of meningitis were observed in three patients and focal signs in four patients. One patient had no neurological signs. The median time between the first cerebral symptoms and diagnosis was 22.4 days (IQR 9.5–36.2). Two patients died within a month after diagnosis. In conclusion, few proven CNS localizations of histoplasmosis were observed on 30-year study in French Guiana. This low proportion suggests that the documentation of CNS involvement is often not ascertained for lack of awareness of this particular presentation, and for lack of rapid and sensitive diagnostic tools.

Central nervous system histoplasmosis in a European immunocompetent patient: A challenging diagnosis.

Central nervous system histoplasmosis in a European immunocompetent patient: A challenging diagnosis.

Cerebral histoplasmosis caused by Histoplasma capsulatum var. duboisii in a patient with no known immunodeficiency.

We report the first case of central nervous system histoplasmosis caused by Histoplasma capsulatum var. duboisii in a patient with no underlying immunodeficiency. African histoplasmosis is an underdiagnosed endemic fungal infection which should be included in the differential diagnosis of cerebral lesions in patients originating from Western and Central Africa.

A Case of Histoplasmosis with Central Nervous System Relapse after Itraconazole Therapy Needs Further Research

Central nervous system (CNS) histoplasmosis occurs in 5-20% of all cases and is most commonly seen in immunosuppressed patients who have acquired immunodeficiency syndrome (AIDS) or have received organ transplant. The prevalence of histoplasmosis in patients greater than 65 years old between the years of 1999-2008 in the state of Texas was about 2-3 cases per 100,000 patients year. Since 1990 with the discovery of Triazoles, itraconazole (ICZ) has become the standard initial and suppressive therapy in patients with mild-moderate histoplasmosis without CNS involvement. However, poor penetration of ICZ into the brain, in vitro fluconazole resistance and lack of controlled-trials pose challenge in the treatment of cerebral histoplasmosis.

Central Nervous System Infection with Histoplasma capsulatum.

Histoplasmosis is an endemic fungal infection that may affect both immune compromised and non-immune compromised individuals. It is now recognized that the geographic range of this organism is larger than previously understood, placing more people at risk. Infection with Histoplasma capsulatum may occur after inhalation of conidia that are aerosolized from the filamentous form of the organism in the environment. Clinical syndromes typically associated with histoplasmosis include acute or chronic pneumonia, chronic cavitary pulmonary infection, or mediastinal fibrosis or lymphadenitis. Disseminated infection can also occur, in which multiple organ systems are affected. In up to 10% of cases, infection of the central nervous system (CNS) with histoplasmosis may occur with or without disseminated infection. In this review, we discuss challenges related to the diagnosis of CNS histoplasmosis and appropriate treatment strategies that can lead to successful outcomes.

Histoplasmosis: Epidemiology, Diagnosis, and Clinical Manifestations

This review highlights the epidemiology, diagnosis, and clinical manifestations of histoplasmosis. There is an increasing awareness of histoplasmosis in Central and South America in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), and deaths from histoplasmosis in this region may outnumber deaths from tuberculosis. Diagnosis in this region is hampered by lack of rapid diagnostic tests. Growth of H. capsulatum in culture is definitive, but takes weeks. In areas in which antigen testing is available, this has become an important rapid diagnostic tool, and methods combining antigen and antibody testing appear to improve diagnostic accuracy for acute pulmonary and central nervous system histoplasmosis. Pulmonary histoplasmosis, although usually self-limited, rarely can lead to life-threatening complications. Uncommon, but serious and sometimes fatal complications of disseminated histoplasmosis include Addison’s disease, meningitis, culture-negative endocarditis, and hemophagocytic lymphohistiocytosis. The use of antigen testing has improved our ability to diagnose histoplasmosis, but these tests are not universally available. Complications of both pulmonary and disseminated histoplasmosis remain challenging.

Central nervous system histoplasmosis: Multicenter retrospective study on clinical features, diagnostic approach and outcome of treatment: Erratum.

Central nervous system (CNS) histoplasmosis is one of the important endemic mycoses in America and Africa. Although the incidence of CNS histplasmosis in non-endemic areas is increasing, the diagnosis of isolated CNS histoplasmosis in these areas remains challenging. Since the diagnosis is often missed, the outcome of CNS histoplasmosis is occasionally poor. One of the important complications of this condition is hydrocephalus, which may be identified before meningitis is diagnosed. Antigen or serological tests are useful for the diagnosis of CNS histoplasmosis; however, it should be noted that false positive results may be obtained because of cross reactions due to infections by other fungi. Further, repeated culture with a large volume of cerebrospinal fluid is essential because of the low sensitivity of culture. Thus, it is recommended that tests for CNS histplasmosis be repeated, even if negative results are obtained initially. Liposomal amphotericin B is the usual initial therapy for CNS histoplasmosis. However, the rate of failure of initial treatment is high and relapse can occur in the next few years, which calls for careful management of patients with CNS histoplasmosis. Continued therapy with antifungal agents such as fluconazole or itraconazole is often required. We report a case of a patient with chronic meningitis in whom the tests for other causes were negative for about 10 years, and who was eventually diagnosed with CNS histoplasmosis. Treatment with fluconazole was initiated, and the patient's symptoms gradually improved. Further cerebrospinal fluid (CSF) analysis and brain computed tomography (CT) during the follow-up period of 2 years and 9 months did not reveal recurrence of meningitis or hydrocephalus, thereby indicating the successful treatment of CNS histoplasmosis with fluconazole. CNS histoplasmosis should always be included in the differential diagnoses of chronic meningitis in non-endemic areas even in the case of immunocompetent individuals.

Central nervous system histoplasmosis: Multicenter retrospective study on clinical features, diagnostic approach and outcome of treatment.

Central nervous system (CNS) involvement occurs in 5 to 10% of individuals with disseminated histoplasmosis. Most experience has been derived from small single center case series, or case report literature reviews. Therefore, a larger study of central nervous system (CNS) histoplasmosis is needed in order to guide the approach to diagnosis, and treatment.A convenience sample of 77 patients with histoplasmosis infection of the CNS was evaluated. Data was collected that focused on recognition of infection, diagnostic techniques, and outcomes of treatment.Twenty nine percent of patients were not immunosuppressed. Histoplasma antigen, or anti-Histoplasma antibodies were detected in the cerebrospinal fluid (CSF) in 75% of patients. One year survival was 75% among patients treated initially with amphotericin B, and was highest with liposomal, or deoxycholate formulations. Mortality was higher in immunocompromised patients, and patients 54 years of age, or older. Six percent of patients relapsed, all of whom had the acquired immunodeficiency syndrome (AIDS), and were poorly adherent with treatment.While CNS histoplasmosis occurred most often in immunocompromised individuals, a significant proportion of patients were previously, healthy. The diagnosis can be established by antigen, and antibody testing of the CSF, and serum, and antigen testing of the urine in most patients. Treatment with liposomal amphotericin B (AMB-L) for at least 1 month; followed by itraconazole for at least 1 year, results in survival among the majority of individuals. Patients should be followed for relapse for at least 1 year, after stopping therapy.

Diagnosis of Central Nervous System Histoplasmosis by Cerebrospinal Fluid EIA Antibody Detection

Diagnosis of Central Nervous System Histoplasmosis by Cerebrospinal Fluid EIA Antibody Detection

Central Nervous System Histoplasmosis in Acquired Immunodeficiency Syndrome

BackgroundInvolvement of the central nervous system (CNS) by Histoplasma capsulatum in AIDS is uncommon and not easily recognized. Materials and MethodsCNS histoplasmosis cases from our institution were identified by a retrospective chart review from 2004-2014. A thorough literature search was performed for additional cases and their characteristics were compared. Clinical findings, treatment and outcomes are discussed. ResultsA total of 5 cases from our institution were identified. They had a clinical presentation that included classic signs of meningitis, often with evidence of disseminated involvement, and was typically severe with important neurological impairment. These cases were treated with antifungal agents, including a lipid amphotericin B formulation and azole drugs, but eventually 3 experienced nonresolution of their disease likely because of lack of adherence to therapy and died from their infection. The clinical presentation, treatment and outcome of these cases did not significantly differ from cases found in the review of the literature. ConclusionsClinicians practicing in endemic areas should be aware of this rare but serious form of histoplasmosis. The recognition of 5 cases of CNS histoplasmosis in AIDS patients from a single institution suggests that histoplasmosis should be included in the differential diagnosis of the CNS complications of AIDS.

Histoplasmosis diseminada progresiva con afectación del sistema nervioso central en un paciente inmunocompetente. Presentación de un caso y revisión de la literatura

Histoplasmosis is a multifaceted condition caused by the dimorphic fungi Histoplasma capsulatum whose infective spores are inhaled and reach the lungs, the primary organ of infection. The meningeal form, considered one of the most serious manifestations of this mycosis, is usually seen in individuals with impaired cellular immunity such as patients with acquired immunodeficiency syndrome, systemic lupus erythematous or solid organ transplantation, and infants given their immunological immaturity. The most common presentation is self-limited and occurs in immunocompetent individuals who have been exposed to high concentrations of conidia and mycelia fragments of the fungi. In those people, the condition is manifested by pulmonary disorders and late dissemination to other organs and systems. We report a case of central nervous system histoplasmosis in an immunocompetent child.

Histoplasmosis in Patients With Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS)

Although discontinuation of suppressive antifungal therapy for acquired immunodeficiency syndrome (AIDS)-associated histoplasmosis is accepted for patients with immunologic recovery, there have been no published studies of this approach in clinical practice, and minimal characterization of individuals who relapse with this disease. We performed a multicenter retrospective cohort study to determine the outcome in AIDS patients following discontinuation of suppressive antifungal therapy for histoplasmosis.Ninety-seven patients were divided into a physician-discontinued suppressive therapy group (PD) (38 patients) and a physician-continued suppressive therapy group (PC) (59 patients). The 2 groups were not statistically different at baseline, but at discontinuation of therapy and at the most recent follow-up there were significant differences in adherence to therapy, human immunodeficiency virus (HIV) RNA, and urinary Histoplasma antigen concentration. There was no relapse or death attributed to histoplasmosis in the PD group compared with 36% relapse (p < 0.0001) and 5% death (p = 0.28) in the PC group. Relapse occurred in 53% of the nonadherent patients but not in the adherent patients (p < 0.0001). Sixty-seven percent of patients with initial central nervous system (CNS) histoplasmosis relapsed compared to 15% of patients without CNS involvement (p = 0.0004), which may be accounted for by nonadherence. In addition, patients with antigenuria above 2.0 ng/mL at 1-year follow-up were 12.82 times (95% confidence interval, 2.91–55.56) more likely to relapse compared to those with antigenuria below 2.0 ng/mL.Discontinuation of antifungal therapy was safe in adherent patients who completed at least 1 year of antifungal treatment, and had CD4 counts >150 cells/mL, HIV RNA <400 c/mL, Histoplasma antigenuria <2 ng/mL (equivalent to <4.0 units in second-generation method), and no CNS histoplasmosis.

Histoplasmosis of the Central Nervous System

Histoplasmosis of the central nervous system (CNS) is not an uncommon complication of Histoplasma capsulatum infection since it occurs in ∼2% to 20% of disseminated cases. CNS histoplasmosis carries a mortality rate that ranges from 11.1% to 100%, and the risk factors for dissemination to the brain have yet to be determined. Diagnosis is often difficult and time consuming, which can result in delayed initiation of treatment. The recommended treatment for CNS histoplasmosis involves a high dose liposomal amphotericin B followed by maintenance azole therapy, usually for at least a year; however no comparative trials have been performed to prove efficacy of one regimen over another. Further, prospective and in vivo studies are necessary to more effectively combat this disease.

Chronic Primary Central Nervous System Histoplasmosis in a Healthy Child With Intermittent Neurological Manifestations

Meningitis is an unusual clinical manifestation of Histoplasma capsulatum infection in nonimmunosuppressed children. We report a previously healthy 6-year-old boy with primary, chronic histoplasma meningitis and magnetic resonance imaging findings consistent with demyelinating disease presenting with brief, intermittent neurological manifestations for 7 months before diagnosis.

Isolated Central Nervous System Histoplasmosis Presenting With Ischemic Pontine Stroke and Meningitis in an Immune-Competent Patient

Histoplasmosis, a systemic mycosis caused by the fungus Histoplasma capsulatum, primarily affects immune-suppressed patients and commonly involves the lung and rarely the central nervous system (CNS). Herein, we report a case of isolated CNS histoplasmosis presenting with pontine stroke and meningitis. A 35-year-old, white, immune-competent man was transferred from an outside facility with worsening dysarthria and confusion after having presented 4 weeks prior with dysarthria, gait ataxia, and bilateral upper extremity weakness. Brain magnetic resonance imaging revealed bilateral pontine strokes, and the working diagnosis was ischemic infarctions, presumed secondary to small vessel vasculitis. Cerebral spinal fluid (CSF) examination showed marked abnormalities including an elevated protein level (320 mg/dL), low glucose level (2 mg/dL), and high white blood cell count (330/mm(3); 28% lymphocytes, 56% neutrophils, and 16% monocytes) suggestive of a bacterial, fungal, or tuberculosis meningitis. Empirical antibiotics and a second trial of intravenous steroids were started before infectious etiologies of meningitis were ultimately ruled out. Repeated magnetic resonance imaging of the brain revealed no evidence of new ischemic lesions. On hospital day 11, results of his CSF Histoplasma antigen and urine antigen tests were positive. His CSF culture also was positive for H capsulatum. The patient was treated initially with liposomal amphotericin B, 430 mg daily, but changed to voriconazole, 300 mg twice daily, secondary to renal insufficiency and eventually continued treatment with itraconazole cyclodextrin, 100 mg twice daily. Computed tomographic imaging revealed obstructive hydrocephalus, and a ventriculoperitoneal shunt was placed that successfully decompressed the ventricles. At 1 year, the patient demonstrated good clinical improvement and results of follow-up CSF cultures were negative. While pulmonary involvement of histoplasmosis in immune-suppressed patients is common, systemic presentation of this fungal infection in immune-competent patients is rare and self-limiting. Isolated CNS histoplasmosis is exceedingly rare. Clinicians should consider CNS histoplasmosis in the differential diagnosis in atypical stroke cases, particularly those presenting with meningitis.

Isolated central nervous system histoplasmosis in an immunocompetent patient: 53-month hiatus to diagnosis and treatment

Isolated central nervous system histoplasmosis in an immunocompetent patient: 53-month hiatus to diagnosis and treatment

Isolated central nervous system histoplasmosis in an immunocompetent patient: 53-month hiatus to diagnosis and treatment

Chronic meningitis may result from a wide range of etiologies, both infectious and noninfectious, and is often diagnostically challenging. In most series, tuberculosis remains the most common recognized cause. Of the fungal diseases resulting in chronic meningitis, Cryptococcus is the most common. When untreated, the infectious meningitides typically exhibit an inexorably progressive course with high morbidity and mortality. We report a patient with chronic meningitis due to Histoplasma capsulatum who exhibited a remarkably benign course despite being untreated for the disorder for more than 4 years.