Elevation of intracranial pressure in acute AIDS-related cryptococcal meningitis

Prior to the AIDS-era, elevation of intracranial pressure was known to be a typical complication of cryptococcal meningitis associated with an increased risk of early death. In AIDS-patients, however, the prevalence and clinical significance of this complication are as yet unclear. We analysed clinical features and courses, CSF findings, serological results and neuroimaging scans in acute cryptococcal meningitis in eight patients with AIDS. Five showed symptoms and signs compatible with raised intracranial pressure, which was life-threatening in one and the most probable cause of death in another. Serial monitoring of intracranial pressure together with repeated CSF analysis revealed that severe intracranial pressure elevation in AIDS related cryptococcal meningitis can occur in spite of effective antimycotic treatment, does not depend on an increased CSF/serum osmolality ratio or CSF overproduction and can be associated with normal cranial computed tomography and magnetic resonance imaging findings. Our data support the hypothesis that CSF reabsorption failure plays the crucial role in the pathophysiological mechanism. External lumbar drainage may be of benefit in selected cases of acute AIDS related cryptococcal meningitis with persisting life threatening elevation in intracranial pressure and normal computed tomogram.Abbreviations AIDS acquired immune deficiency syndrome - CM cryptococcal meningitis - CSF cerebrospinal fluid - CT computed tomography - HIV human immunodeficiency virus - ICP intracranial pressure - MRI magnetic resonance imaging Correspondence to: R. Malessa     

Prediction of unfavorable outcomes in cryptococcal meningitis: results of the multicenter Infectious Diseases International Research Initiative (ID-IRI) cryptococcal meningitis study

Cryptococcal meningitis (CM) is mostly seen in immunocompromised patients, particularly human immunodeficiency virus (HIV)-positive patients, but CM may also occur in apparently immunocompetent individuals. Outcome analyses have been performed in such patients but, due to the high prevalence of HIV infection worldwide, CM patients today may be admitted to hospitals with unknown HIV status, particularly in underdeveloped countries. The objective of this multicenter study was to analyze all types of CM cases in an aggregate cohort to disclose unfavorable outcomes. We retrospectively reviewed the hospitalized CM patients from 2000 to 2015 in 26 medical centers from 11 countries. Demographics, clinical, microbiological, radiological, therapeutic data, and outcomes were included. Death, neurological sequelae, or relapse were unfavorable outcomes. Seventy (43.8%) out of 160 study cases were identified as unfavorable and 104 (65%) were HIV infected. On multivariate analysis, the higher Glasgow Coma Scale (GCS) scores (p?=?0.021), cerebrospinal fluid (CSF) leukocyte counts > 20 (p?=?0.038), and higher CSF glucose levels (p?=?0.048) were associated with favorable outcomes. On the other hand, malignancy (p?=?0.026) was associated with poor outcomes. Although all CM patients require prompt and rational fungal management, those with significant risks for poor outcomes need to be closely monitored.     

D-mannitol in cerebrospinal fluid of patients with AIDS and cryptococcal meningitis.

Cryptococcal meningitis (CM) is associated with raised intracranial pressure which is linked with serious neurological sequelae. Cryptococcus neoformans produces D-mannitol in vitro and in experimental meningitis in rabbits. Mannitol present in the cerebrospinal fluid (CSF) of CM patients could exacerbate raised intracranial pressure and contribute to neurological damage. To link CSF mannitol to cryptococcal infection, levels of mannitol in the CSF of AIDS patients with CM were measured by gas-liquid chromatography. Mannitol was detected in 19 of 21 samples (range, 1.5 to 26.2 mg/liter), but there was no quantitative correlation between the mannitol concentration and the cryptococcal antigen titer.     

Prognostic significance of serum antioxidant parameters in immunocompetent patients with cryptococcal meningitis

The purpose of this investigation was to determine whether endogenous antioxidants were prognostic factors in immunocompetent patients with cryptococcal meningitis (CM). The clinical features, alterations of serum albumin, bilirubin, and uric acid (UA) levels before and after six weeks of treatment in 94 immunocompetent patients with CM from January 2000 to December 2010 were retrospectively analyzed. The patients with CM had lower serum albumin and UA levels and higher bilirubin levels before treatment. After six weeks of treatment, the serum bilirubin levels decreased significantly and the serum UA levels increased significantly in 'cured/improved' patients. The serum UA level was negatively correlated with log cerebrospinal fluid (CSF) cryptococcal count and positively correlated with the CSF glucose level. A significantly lower level of serum UA was associated with high CSF open pressure, hydrocephalus, brain lesions, and consciousness disturbance. Moreover, the good outcome was 7.779 times more likely to occur in patients with an increase in the serum UA level ≥38.8% after six weeks of treatment. A logistic regression analysis also confirmed that an increase in the serum UA level ≥38.8% after six weeks of treatment was an independent good outcome predictor. Though there were abnormal conditions of serum antioxidants, the variation in the UA level could serve as a potential indicator of therapeutic efficacy in immunocompetent patients with CM.     

Review: The application of corticosteroids in cryptococcal meningitis

Cryptococcal meningitis (CM) is a serious disease with high morbidity and mortality. Although the patients who received corticosteroids were at high risk of having CM, corticosteroids also have been used as an adjunct to antifungal drugs for treating people with CM in some situations (such as immune reconstitution inflammatory syndrome, cerebral cyptococcoma, et al.). Here, we summarize the current knowledge on the application of the corticosteroids in CM, aiming to help clinicians to reasonably use corticosteroids in patients with CM.     

Clinical profile and outcome of non-HIV-infected patients with cryptococcal meningitis and malignancy

BackgroundCryptococcal meningitis (CM) can coexist with malignancy in patients not infected by human immunodeficiency virus (HIV). The purpose of this study was to evaluate the clinical characteristics and therapeutic outcomes of non-HIV-infected patients with CM with malignancy.MethodsThe study cohort comprised 320 patients diagnosed with CM from January 2013 to May 2019. Malignancy was diagnosed based on the medical history, imaging findings, and pathological findings. One-hundred-and-four patients also underwent positron emission computed tomography (PET-CT) examination to enable the early detection of possible malignancies. The demographics, clinical characteristics, and outcomes were analyzed.ResultsTwelve patients with CM with malignancies were found. Seven were patients with CM who had a history of malignancies (CM in malignancy; CIM), while five patients had malignancies detected after being diagnosed with CM (malignancy in CM; MIC). The patients with CM with malignancies, especially MIC, were older than those without malignancies. The outcome was similar for patients with CIM and patients with CM without malignancy, but was extremely poor for patients with MIC. PET-CT examination suggested malignancy in five of 104 patients, with malignancy finally confirmed in four of five patients.ConclusionsCompared with the general population, the rate of solid malignancies was increased in patients with CM, especially older adults. The presence of malignancies and timing of discovery were closely related to the outcome of patients with CM. Thus, it is necessary to screen for malignancies in older adults with CM. PET-CT might be useful for early malignancy screening of patients with CM.     

Possibility of diagnosing meningitis by gas chromatography: cryptococcal meningitis.

Cerebrospinal fluid (CSF) from eight patients with cryptococcal meningitis, from ten patients with viral meningitis, and from four control patients without meningitis were analyzed by electron-capture gas-liquid chromatography (EC-GLC). All cryptococcal specimens had similar EC-GLC profiles, and these differed from those of the controls. Viral EC-GLC patterns were different from those obtained with specimens from the patients with cryptococcal infection and from the controls. In addition, specimens from patients with various types of viral infections gave profiles that differed from each other. Two normal CSFs were inoculated with Cryptococcus neoformans; aliquots of these cultures showed an EC-GLC pattern very similar to that seen in CSF of patients with cryptococcal meningitis. The EC-GLC procedure is rapid, reproducible, and easy to perform and may hold promise as an additional aid in the diagnosis of cryptococcal infection.     

Risk factors and outcomes of cerebrospinal fluid overdrainage in HIV-negative patients with cryptococcal meningitis after the ventriculoperitoneal shunting procedure

Purpose

Shunt procedures used to treat cryptococcal meningitis complicated with hydrocephalus and/or increased intracranial pressure (IICP) could result in cerebrospinal fluid (CSF) overdrainage, thereby presenting therapeutic challenges.

A retrospective research of HIV-negative cryptococcal meningoencephalitis patients with acute/subacute onset

Cryptococcal meningoencephalitis (CM) may present as an acute, subacute, or chronic infection. It manifests as a chronic process in over 75 % of cases, but, sometimes, it presents with a more acute onset, mostly in HIV-associated patients. Until now, there has been no study performed on the clinical features of HIV-negative CM patients with acute/subacute onset. We collected 106 HIV-negative patients diagnosed with CM in our hospital during a 15-year period, analyzed their epidemiological and clinical features, as well as the outcomes, and explored the independent prognosis factors and the factors related to the survival time among them. We found that impaired consciousness (23.4 % vs. 3.4 %, p?=?0.017) was more common in CM patients with acute/subacute onset, while decreased cerebrospinal fluid (CSF) glucose (51.9 % vs. 75.9 %, p?=?0.026) was less common. The ratio of CSF glucose/blood glucose [odds ratio (OR) 0.04, 95 % confidence interval (CI) 0.004–0.262, p?=?0.02], impaired consciousness (OR 5.09, 95 % CI 1.477–17.522, p?=?0.01), and hospitalization length (OR 0.98, 95 % CI 0.977–0.999, p?=?0.04) were indicated to be not only independent prognosis factors in HIV-negative CM patients with acute/subacute onset, but also factors significantly related to the survival time. The results of our study demonstrated that the contact history and potential history risk factors would not affect the onset process of HIV-negative CM patients, and the mortality, hospitalization length, and survival time has not been related to the onset process. However, the ratio of CSF glucose/blood glucose, consciousness level, and hospitalization length of the HIV-negative CM patients with acute/subacute onset should be of greater focus in the clinical work.     

Neurologic Manifestations of Enterovirus 71 Infection in Korea

Enterovirus 71 frequently involves the central nervous system and may present with a variety of neurologic manifestations. Here, we aimed to describe the clinical features, magnetic resonance imaging (MRI) findings, and cerebrospinal fluid (CSF) profiles of patients presenting with neurologic complications of enterovirus 71 infection. We retrospectively reviewed the records of 31 pediatric patients hospitalized with acute neurologic manifestations accompanied by confirmed enterovirus 71 infection at Ulsan University Hospital between 2010 and 2014. The patients’ mean age was 2.9 ± 5.5 years (range, 18 days to 12 years), and 80.6% of patients were less than 4 years old. Based on their clinical features, the patients were classified into 4 clinical groups: brainstem encephalitis (n = 21), meningitis (n = 7), encephalitis (n = 2), and acute flaccid paralysis (n = 1). The common neurologic symptoms included myoclonus (58.1%), lethargy (54.8%), irritability (54.8%), vomiting (48.4%), ataxia (38.7%), and tremor (35.5%). Twenty-five patients underwent an MRI scan; of these, 14 (56.0%) revealed the characteristic increased T2 signal intensity in the posterior region of the brainstem and bilateral cerebellar dentate nuclei. Twenty-six of 30 patients (86.7%) showed CSF pleocytosis. Thirty patients (96.8%) recovered completely without any neurologic deficits; one patient (3.2%) died due to pulmonary hemorrhage and shock. In the present study, brainstem encephalitis was the most common neurologic manifestation of enterovirus 71 infection. The characteristic clinical symptoms such as myoclonus, ataxia, and tremor in conjunction with CSF pleocytosis and brainstem lesions on MR images are pathognomonic for diagnosis of neurologic involvement by enterovirus 71 infection.     

New-onset seizures in patients with immunodeficiency virus infection in Bobo-Dioulasso Hospital (Burkina Faso)

Seizures are common in advanced stages of immunodeficiency virus (HIV) infection. HIV-infected outpatients and inpatients in the national hospital in Bobo-Dioulasso among whom seizures occurred had been recruited over four years. There were mainly male (30/13) with an average age of 35 years with extremes ranging from 22 to 60 years. New-onset generalised seizures occurred in all cases of cryptococcal meningitis or partial motor secondary generalised in 64% among patients with suspected cerebral toxoplasmosis due to the efficiency of the treatment of the antitoxoplasmic proof. Identified causes such as suspected cerebral toxoplasmosis (65%), suspected tuberculous meningitis (7%) as CSF culture is not available, cryptococcal meningitis (16%) were found in this study. In four cases among 43 patients, no identified causes could be determined. CD4 lymphocytes count which was available in 24 patients was under 200/41 in 74% of the cases. This study indicates clearly that seizures in young adults are strongly associated with focal brain lesions and cerebral toxoplasmosis is becoming an important cause of seizure in tropical area. This should imply a screening of toxoplasmosis with new-onset seizure in young people.     

Discontinuation of maintenance therapy against toxoplasma encephalitis in AIDS patients with sustained response to anti-retroviral therapy

Discontinuation of maintenance therapy against toxoplasma encephalitis (TE) for individuals infected with human immunodeficiency virus (HIV) who are receiving successful anti-retroviral therapy is considered safe. Nevertheless, there are few published studies concerning this issue. Within the setting of the Swiss HIV Cohort Study, this report describes a prospective study of discontinuation of maintenance therapy against TE in patients with a sustained increase of CD4 counts to > 200 cells/microL and 14% of total lymphocytes, and no active lesions on cerebral magnetic resonance imaging (MRI). In addition to clinical evaluation, cerebral MRI was performed at baseline, and 1 and 6 months following discontinuation. Twenty-six AIDS patients with a history of TE agreed to participate, but three patients (11%) could not be enrolled because they still showed enhancing cerebral lesions without a clinical correlate. One patient refused MRI after 6 months while clinically asymptomatic. Among the remaining 22 patients who discontinued maintenance therapy, one relapsed after 3 months. During a total follow-up of 58 patient-years, there was no TE relapse among the patients who had remained clinically and radiologically free of relapse during the study. Thus, discontinuation of maintenance therapy against TE was generally safe, but may fail in a minority of patients. Patients who remain clinically and radiologically free of relapse at 6 months after discontinuation are unlikely to experience a relapse of TE.     

Commercial cryptococcal latex kit: clinical evaluation in a medical center hospital.

A commercial latex kit for the detection of cryptococcal antigen (LCAT) was used in a medical center hospital to test cerebrospinal fluid (CSF) and serum specimens from patients suspected of having cryptococcal infections. The LCAT was also performed on 8 CSF and 2 serum specimens from other mycotic infections and on 50 serum specimens from healthy controls. Of a total of 561 specimens (489 CSF and 72 sera) from 426 patients, 78 (13.9%) specimens were LCAT positive; these came from 12 patients with culturally proven cryptococcosis. Eleven of these 12 patients were diagnosed as having disseminated cryptococcosis (9 with meningitis). Fourteen other patients, all with positive cultures for Cryptococcus neoformans but nevative LCATs on sera or CSF, were found not to have disseminated infections. All CSF and sera from other mycotic infections and all 50 control sera were negative. No false positive or flase negative tests were encountered. It was concluded that the commercial kit is useful for diagnosis and prognosis of disseminated cryptococcosis, but not as useful for infections such as localized pulmonary or cutaneous cryptococcosis.     

Coagglutination (COA) test for the rapid diagnosis of cryptococcal meningitis

Cryptococcus coagglutination (COA) test reagent was prepared locally and showed no cross reactions with different species of bacteria or yeasts or with 75 control sera including 25 that gave positive results for RA factor. We used the COA test to detect cryptococcus antigen in the CSF and we could confirm the diagnosis of 11 out of 115 suspected cases of fungal meningitis; the titre varied from 4 to 128. A four-fold rise in titre confirmed the diagnostic value and a steady fall in titre in three patients on therapy indicated the prognostic value of the test. The earliest confirmation was in a renal transplant patient on the eighth day after onset of symptoms. The COA test was negative with the CSF of 118 patients with chronic meningitis. Cryptococcal colony forming units (cfu) in CSF varied from 100 to greater than 100,000/ml and correlated well with microscopy and with the COA antigen titre in CSF. Four out of the 11 patients who had cryptococcaemia, had 50,000-100,000 cfu/ml in the CSF. Cryptococcus antigen was detected by COA in the serum of all 11 patients, even in those with only 100 cfu/ml in CSF. In the three post-renal transplant patients, who were being monitored regularly, the diagnosis was made early and all three recovered on antifungal therapy with no relapse to date (1-2 years). All the others, including the two primary CNS infections, succumbed to the disease because they presented late for diagnosis and therapy. The cryptococcus COA test is a simple and specific test that can be used as a rapid test to confirm early diagnosis and permit prompt therapy, which should improve the prognosis in CNS and other forms of systemic cryptococcosis. Moreover, it is reproducible and cost-effective, particularly in countries where the latex and other expensive test reagents are not generally available.     

Changing paradigm of Cryptococcal meningitis: An eight-year experience from a tertiary hospital in South India

Background: Cryptococcal meningitis (CM) is a common opportunistic fungal infection causing sub-acute meningitis with the potential for complications and significant mortality. We conducted this study to describe the difference in presentation and outcome between HIV-infected and HIV-uninfected patients. Materials and Methods: Patients admitted to a tertiary care centre between 2005 and 2013 with confirmed CM were included in the analysis. Details of the clinical presentation, laboratory findings, treatment details, risk factors for infection and outcome were documented and analysed. Results: During the study period, 102 (87.2%) cases of CM occurred among HIV infected individuals, whereas 15 (12.8%) occurred among HIV-uninfected patients. HIV-infected patients with CM were younger compared with HIV-uninfected patients (38.2 ± 8.5 years vs. 45 ± 11.5 years; P = 0.07). The median duration of symptoms prior to presentation was shorter in the HIV-infected group (20 ± 32 vs. 30 ± 42; P = 0.03). There was no difference between the cerebrospinal fluid (CSF) lymphocyte counts, CSF protein counts, and CSF sugar levels in both the groups. The diagnostic yield of Cryptococcus was similar with CSF India ink smear (89% vs. 87%), CSF fungal culture (95% vs. 87%), and blood culture (100% vs. 75%) in both the groups. Case fatality rate in the HIV-infected group was 30.6%, whereas there were no deaths in the HIV-uninfected group. Conclusion: HIV-infected patients with CM have a worse outcome compared to HIV-uninfected patients. The overall trend over 3 decades shows increasingly successful rates of treatment and hence early diagnosis and treatment are of paramount importance.     

Effects of melanotan II, a melanocortin agonist, on grooming and exploration in rats after repeated restraint/immobilization

We wanted to verify the magnetic resonance imaging (MRI) abnormalities that occur in the central nervous system (CNS) of cobalamin-deficient (Cbl-D) rats. The rats were made Cbl-D by means of total gastrectomy or feeding a Cbl-D diet. MR images of the cervical tract of the vertebral canal were recorded using a vertical spectrometer, and the volume of cerebrospinal fluid (CSF) in this part of the vertebral canal was calculated. The findings of the present study demonstrate that: (i) there was a significant decrease in cervical tract CSF volume regardless of the way in which the vitamin deficiency was induced; (ii) this volume normalized in the totally gastrectomized rats after chronic Cbl treatment; (iii) no blood-brain or blood-CSF barrier lesions were found in Cbl-D rats, using either MRI with a paramagnetic contrast agent or calculating the albumin CSF/serum concentration quotient. Cbl deficiency decreases CSF volume in the cervical tract of the vertebral canal of the rat, without apparently impairing the blood-brain barrier.     

Adenosine deaminase activity in cerebrospinal fluid of HIV-infected patients: limited value for diagnosis of tuberculous meningitis

Adenosine deaminase activity (ADA) determination in cerebrospinal fluid (CSF) is considered a specific test for the diagnosis of tuberculous meningitis. In order to study the variability of this marker in patients with different neurological disorders associated with HIV infection, and its utility for the diagnosis of tuberculous meningitis in these patients, the ADA levels in 417 CSF samples from HIV-infected patients with neurological symptoms were reviewed. HIV infection, HIV-associated neurological disorders, and progressive multifocal leukoencephalopathy were not associated with elevated ADA in CSF. Among patients with meningitis, receiver operating characteristic curve analysis gave an optimal ADA cut-off point of 8.5 IU/l for the diagnosis of tuberculous meningitis, with 57% sensitivity, 87% specificity, and an area under the curve of 0.747 (similar to that for CSF glucose concentration). False-positive results were found in patients with neurological CMV disease and cryptococcal, lymphomatous, and probable candidal meningitis. The results of this study indicate that ADA determination in CSF has limited utility for the diagnosis of tuberculous meningitis in HIV-infected patients.     

Cryptococcus meningitis and skin lesions in an HIV negative child

Disseminated cryptococcosis is an uncommon occurrence in immunocompetent populations and occurs mainly in immunocompromised patients. The first case of cryptococcus meningitis and skin lesions in a 4-year-old confirmed HIV negative boy who presented with fever, meningism and skin lesions is reported. On examination the child was confused, uncooperative, and had neck stiffness and raised skin lesions. A septic screen, including skin scraping, was performed; the child was treated with penicillin and ceftriaxone for suspected meningococcal meningitis. The cerebrospinal fluid (CSF) had normal protein, glucose and chloride levels; yeasts were observed on Gram stain from the CSF and skin scraping. The India ink stain and Cryptococcus neoformans latex agglutination test on the CSF were both positive. Bacterial culture of the skin biopsy, CSF and blood culture specimens was negative. The child was treated with amphotericin B based on preliminary results, and had a gradual recovery with no neurological sequelae. The child continued oral fluconazole.     

Prevalence of fungal meningitis among HIV positive & negative subjects in Indore (MP state)

The aim of the study was to find out the prevalence of fungal meningitis among AIDS cases and to assess the prognosis of fungal meningitis among HIV positive & negative subjects. The study comprised of 15 & 10 cases of fungal meningitis among HIV positive & negative subjects respectively during the study period 1992-2001. India ink preparation and Gram's staining procedures were carried out on the centrifuged CSF deposits. The CSF deposits were also used for bacterial and fungal culture. In the present study the prevalence of fungal meningitis was noted among 15 (3.1%) of 483 AIDS cases. Twelve of them had cryptococcal meningitis while 3 were infected with Candida albicans. Four AIDS cases presented fungal meningitis as a primary opportunistic infection and HIV status was confirmed in 4 of them after the diagnosis of fungal meningitis. 13 of the 15 cases were in the age group 26-40 yrs while one was 55 yrs old and the other 16 month old child; these two cases had blood transfusion transmitted and vertically transmitted mode of HIV transmission respectively. Further, only two of 15 cases were females and both acquired HIV infection through blood transfusion. Overall prognosis of fungal meningitis was poor among HIV positives and 7 of the 15 cases died in hospital within 2-3 weeks after diagnosis of cryptococcal meningitis. Among HIV negative subjects, ten cases of fungal meningitis (3 with Candida albicans and 7 with Cryptococcous neoformans) were noted at our end and nine of them had immunocompromised status (3 cases of renal transplant on immunosuppressives, 3 cases neonates/infant and 2 diabetic subjects. The fungal meningitis is one of the important causes of morbidity & mortality among immunocompromised among HIV positive subjects.     

Middle cerebral artery territory infarct due to Cryptococcus infectionstitle

Cryptococcal meningitis is the most common manifestation of cryptococcosis and is caused by the encapsulated yeast organism Cryptococcus neoformans. It occurs most commonly in patients with impaired cell‐mediated immunity such as in HIV infection; patients with hematological malignancies; patients post solid‐organ transplantation; on chronic steroids or immunosuppressants. Clinically, stroke can arise as a complication of cryptococcal meningitis. While cerebrospinal fluid (CSF) examination is usually not indicated for evaluation of stroke patients, demonstration of cryptococcal yeast forms in CSF is valuable in guiding appropriate therapy in arterial stroke caused by Cryptococci. Herein, we describe the CSF and radiologic correlation in a female patient who presented with disseminated cryptococcosis, cryptococcal meninigitis and a middle cerebral artery infarct. Diagn. Cytopathol. 2015;43:632–634. © 2014 Wiley Periodicals, Inc.