Cryptococcal Meningoencephalitis Research Articles

Spectrum of Cryptococcal Meningoencephalitis in Tertiary Hospital in Nepal

Spectrum of Cryptococcal Meningoencephalitis in Tertiary Hospital in Nepal

Predictors of Fatal Outcome in Newly Diagnosed Tuberculosis/HIV Co-Infection with Chronic Alcoholism (Clinical Case)

Our own case of tuberculosis/HIV co-infection’s diagnosis in chronic alcoholism and analysis of the fatal outcome predictors are presented. The patient abused alcohol for a long time in the presented case, he was hospitalised with acute psychosis in a psychoneurological dispensary, where pulmonary tuberculosis and HIV infection were diagnosed for the first time during additional examination. The patient was admitted to the department in serious condition after prolonged alcohol intoxication. The patient’s condition stabilized after detoxification therapy. Antimycobacterial therapy according to the scheme of an individual treatment regimen, antiretroviral therapy, treatment of hepatitis B and C, detoxification therapy, prophylaxis with Biseptol and Fluconazole and symptomatic therapy were prescribed. After 20 days immune reconstitution inflammatory syndrome developed. It was manifested with meningitis and cryptococci were detected in the cerebrospinal fluid 17 days later. Prescribed treatment of cryptococcal meningoencephalitis with fluconazole in high doses intravenously had a significant positive effect, which made it possible to reduce the dose of the drug to the maintenance level. The treatment was not stopped, but sterility of the liquor was not achieved. After 98 days the patient entered a coma and after 113 days he died from the progression of multiple organ failure and cryptococcal meningitis. It should be noted that the patient was diagnosed with tuberculosis with multiple drug resistance for the first time, the treatment of which had positive dynamics, despite the progression of multiple organ failure and the presence of cryptococcal meningoencephalitis. Therefore, although tuberculosis was not the direct cause of the patient’s death, the disease itself deepened the severity of the general condition. Considering the presented clinical case, it was established that predictors of the fatal outcome of newly diagnosed tuberculosis/HIV co-infection in chronic alcoholism are: antisocial lifestyle; concomitant diseases (tuberculosis, chronic viral hepatitis B and C); cryptococcal meningoencephalitis; fever, altered mental status, cryptococci in the cerebrospinal fluid; the number of CD4+ lymphocytes is less than 200/μL; lack of early screening for CrAg; early initiation of antiretroviral therapy before the diagnosis of cryptococcal meningoencephalitis, which provokes immune reconstitution inflammatory syndrome, against the background of which cryptococcal infection progresses; monotherapy of cryptococcal meningoencephalitis with Fluconazole. Knowledge and practice gaps among medical practitioners contribute to the high fatality rate of cryptococcal meningoencephalitis in tuberculosis/HIV co-infection in chronic alcoholism.

Cryptococcal meningoencephalitis in an immunocompetent host presenting with severe agitation: a case report

Cryptococcal meningoencephalitis in an immunocompetent host presenting with severe agitation: a case report

Brain magnetic resonance imaging and computed tomography findings in cats and dogs with central nervous system cryptococcosis in Australia: 23 cases (2009-2020).

To describe the imaging findings in Australian cats and dogs with CNS cryptococcosis. 23 cases (10 cats; 13 dogs) with CNS cryptococcosis and brain MRI or CT studies available to review. Retrospective, multi-institutional case series. Brain MRI or CT studies were reviewed by a board-certified radiologist. Imaging findings were described and the differences between cats and dogs explored. Morphologic features were consistent with extra-axial lesions in all (n = 13) dogs and either intra-axial (5/10) or extra-axial (4/10) lesions in cats, with 1 cat having no detectable lesions in low-field brain MRI scans. Meningeal abnormalities were most common, followed by forebrain and cerebellar lesions. Intracranial MRI lesions were typically T2 hyperintense and T1 hypo- to isointense. Four cases had T2 hypointense lesions affecting the brain, sinonasal cavity, or regional lymph nodes. Intracranial CT lesions were mostly soft tissue attenuating. Contrast enhancement was present in all cases with contrast series available, with ring enhancement shown only in cats. Osteolysis was more common in dogs than cats, particularly affecting the cribriform plate. All 13 dogs and many (6/10) cats had at least 1 lesion affecting sinonasal or contiguous tissues, and locoregional lymphadenomegaly was common (7/10 cats; 11/13 dogs). Imaging lesions in cryptococcal meningoencephalitis were extra-axial in dogs but could be intra-axial or extra-axial in cats. Careful examination for extracranial lesions (sinonasal, retrobulbar, facial soft tissue, tympanic bullae, or locoregional lymph nodes) is important to provide alternative safe biopsy sites. T2 hypointense lesions, while rare, should prompt consideration of cryptococcosis.

From Widespread to Tailored Antifungal Prophylaxis in Lymphoma Patients Treated with CD19 CAR T- Cell Therapy: Less Is Better

Introduction: Invasive fungal infections (IFI) are a major threat in patients with hematological malignancies with substantial associated morbidity. Patients who receive CD19 CAR T-cell therapy have multiple immune defects that may predispose them to IFI. However, the role and duration of antifungal prophylaxis in this population is debated. Methods: This retrospective study at Memorial Sloan Kettering Cancer Center (MSK) describes the characteristics of antifungal prophylaxis and the frequency of IFI after CD19 CAR T-cell therapy in patients with R/R B-cell lymphoma. Two groups of patients were analyzed. Group A (2016-2020): patients primarily received fluconazole, as clinically indicated, regardless of clinical risk profile; Group B (2020-2023) standard guidelines were established in 2020 with antifungal prophylaxis recommended only in high-risk patients with prolonged neutropenia (≥ 3 weeks), those on systemic steroids (≥0.5 mg/kg/day of prednisone equivalent) for ≥ 3 days, or in patients with previous IFI; patients were treated based on a more restrictive mold-active and patient-tailored prophylactic strategy. Results: Three hundred thirty-two patients treated with CAR T-cell therapy for R/R lymphoma between 2016 and 2023 were analyzed. Group A was comprised of 144 patients, whereas group B had 188 patients. Patients' characteristics are described in Table 1. Overall antifungal prophylaxis was prescribed in 95 (66.4%) and 58 (30.9%) patients in group A and B, respectively. While fluconazole was most frequently given in both groups, there was 50% less use in group B (Figure 1). Anti-mold azoles were prescribed in 8.4% of group A patients, whereas for group B, it increased to 34.5%. In group A, a switch to another antifungal was observed in 42 (29%) patients, mainly to micafungin because of transaminitis with azoles. In group B, 21 (11.2%) patients switched their first antifungal drug, mainly from fluconazole or micafungin to a mold-active agent following updated guidelines. Median duration of grade IV neutropenia was 9 days (range 1-93) for group A and 12 days (range 1-90) for group B. Grade IV neutropenia was present at the start of prophylaxis in 30 (31.5%) patients in group A and 30 (51.7%) patients in group B. In the subgroup of patients without prophylaxis, only 13% in group A and 4% in group B were neutropenic. Bridging therapy was administered in 70% of patients in group A and 80% in group B. IFI infections after CAR T-cell therapy were rare: one patient had cryptococcal meningoencephalitis in group A (0.7%) and one had invasive aspergillosis in group B (0.5%), both on micafungin prophylaxis, not effective on molds and cryptococcus. These results show better rates for IFI compared to the FDA adverse events reporting system (FAERS) database: which is 3.1% considering the same CAR-T products. All-cause mortality was similar between both groups (A: 29.8% vs B: 35.7%). Conclusion: This large single-center cohort of R/R lymphoma patients after CAR T-cell therapy offers a valuable snapshot of two different antifungal prophylactic approaches with remarkably low rates of IFI in both strategies, even after the 2020 guideline update with more restrictive antifungal use. Given the risk of toxicity, drug-drug interactions, and concerns for emerging antifungal resistance with azoles, a restrictive prophylactic strategy seems the best choice in this setting.

A multi-arm, parallel, preclinical study investigating the potential benefits of acetazolamide, candesartan, and triciribine in combination with fluconazole for the treatment of cryptococcal meningoencephalitis

Cryptococcus neoformans, an opportunistic fungal pathogen, primarily infects immunodeficient patients frequently causing cryptococcal meningoencephalitis (CM). Increased intracranial pressure (ICP) is a serious complication responsible for increased morbidity and mortality in CM patients. Non-invasive pharmacological agents that mitigate ICP could be beneficial in treating CM patients. The objective of the study was to investigate the efficacy of acetazolamide (AZA), candesartan (CAN), and triciribine (TCBN), in combination with the antifungal fluconazole, on C. neoformans-induced endothelial, brain, and lung injury in an experimental mouse model of CM. Our study shows that C. neoformans increases the expression of brain endothelial cell (BEC) junction proteins Claudin-5 (Cldn5) and VE-Cadherin to induce pathological cell-barrier remodeling and gap formation associated with increased Akt and p38 MAPK activation. All three agents inhibited C. neoformans-induced endothelial gap formation, only CAN and TCBN significantly reduced C. neoformans-induced Cldn5 expression, and only TCBN was effective in inhibiting Akt and p38MAPK. Interestingly, although C. neoformans did not cause brain or lung edema in mice, it induced lung and brain injuries, which were significantly reversed by AZA, CAN, or TCBN. Our study provides novel insights into the direct effects of C. neoformans on BECs in vitro, and the potential benefits of using AZA, CAN, or TCBN in the management of CM patients.

Cryptococcal Meningoencephalitis in Phenotypically Normal Patients.

Cryptococcosis is an invasive fungal infection found worldwide that causes significant morbidity and mortality among a broad range of hosts. There are approximately 223,000 new cases of cryptococcosis annually throughout the world, and at least 180,000 deaths are attributed to this infection each year. Most of these are due to complications of cryptococcal meningoencephalitis among HIV-infected patients in resource-limited environments. The majority of individuals diagnosed with cryptococcosis have underlying conditions associated with immune dysfunction such as HIV, solid organ transplant, hematologic malignancy, organ failure syndromes, and/or the use of immunosuppressive agents such as glucocorticosteroids and biologic agents. In most clinical series, there is a small proportion of patients with cryptococcosis who are phenotypically normal; that is, they have no clinically obvious predisposition to disease. Cryptococcal meningoencephalitis (CME) presentation and management differ substantially between these normal individuals and their immunocompromised counterparts. In this review, we will focus on CME in the phenotypically normal host and underscore differences in the clinical presentation, management, outcome, and potential risk factors for these patients compared to immunocompromised persons who develop this potential devastating invasive fungal infection.

Author Response: Teaching NeuroImage: Cryptococcal Meningoencephalitis With Cryptococcoma and Gelatinous Pseudocysts.

Author Response: Teaching NeuroImage: Cryptococcal Meningoencephalitis With Cryptococcoma and Gelatinous Pseudocysts.

Shared and unique antibody and B cell profiles in HIV-positive and HIV-negative individuals with cryptococcal meningoencephalitis.

Host non-T cell markers to aid in the diagnosis of cryptococcal meningoencephalitis (CM) have not been identified. In this case-control study, we characterized antibody and B cell profiles in HIV-negative and HIV-positive Vietnamese individuals of the Kinh ethnicity recently diagnosed with CM and controls. The study included 60 HIV-negative with no known immunocompromising condition and 60 HIV-positive individuals, with 30 CM cases and 30 controls in each group. Participants were matched by age, sex, HIV serostatus, and CD4 count in the HIV-positive group. Plasma immunoglobulin (Ig) levels, including IgG1, IgG2, IgM, and IgA, Cryptococcus spp. glucuronoxylomannan (GXM)- and laminarin (branched ${\rm{\beta }}$-[1-3]-glucan)-binding IgG, IgM, IgA levels, and peripheral blood B cell subsets were measured. Logistic regression, principal component, and mediation analyses were conducted to assess associations between antibody, B cell levels, and CM. The results showed that GXM-IgG levels were higher and IgG1 and IgG2 were lower in CM cases than controls, regardless of HIV status. In HIV-negative individuals, IgG2 mediated an inverse association between CD19+CD27+CD43+CD5- (B-1b-like) cells and CM. In HIV-positive individuals, lower levels of IgA, laminarin-IgA, and CD19+CD27+IgM+IgD- (IgM+ memory B) cells were each associated with CM. The shared and distinct antibody and B cell profiles identified in HIV-negative and HIV-positive CM cases may inform the identification of non-T-cell markers of CM risk or unsuspected disease, particularly in HIV-negative individuals.

Palmitoylethanolamide shows limited efficacy in controlling cerebral cryptococcosis in vivo.

Cryptococcus neoformans (Cn) is an encapsulated neurotropic fungal pathogen and the causative agent of cryptococcal meningoencephalitis (CME) in humans. Recommended treatment for CME is Amphotericin B (AmpB) and 5-fluorocytosine (5-FC). Though effective, AmpB has displayed numerous adverse side effects due to its potency and nephrotoxicity, prompting investigation into alternative treatments. Palmitoylethanolamide (PEA) is an immunomodulatory compound capable of promoting neuroprotection and reducing inflammation. To investigate the efficacy of PEA as a therapeutic alternative for CME, we intracerebrally infected mice with Cn and treated them with PEA or AmpB alone or in combination. Our results demonstrate that PEA alone does not significantly prolong survival nor reduce fungal burden, but when combined with AmpB, PEA exerts an additive effect and promotes both survivability and fungal clearance. However, we compared this combination to traditional AmpB and 5-FC treatment in a survivability study and observed lower efficacy. Overall, our study revealed that PEA alone is not effective as an antifungal agent in the treatment of CME. Importantly, we describe the therapeutic capability of PEA in the context of Cn infection and show that its immunomodulatory properties may confer limited protection when combined with an effective fungicidal agent.

Pharmacodynamics of ATI-2307 in a rabbit model of cryptococcal meningoencephalitis.

Cryptococcal meningoencephalitis (CM) is a devastating fungal disease with high morbidity and mortality. The current regimen that is standard-of-care involves a combination of three different drugs administered for up to one year. There is a critical need for new therapies due to both toxicity and inadequate fungicidal activity of the currently available antifungal drugs. ATI-2307 is a novel aryl amidine that disrupts the mitochondrial membrane potential and inhibits the respiratory chain complexes of fungi-it thus represents a new mechanism for direct antifungal action. Furthermore, ATI-2307 selectively targets fungal mitochondria via a fungal-specific transporter that is not present in mammalian cells. It has very potent in vitro anticryptococcal activity. In this study, the efficacy of ATI-2307 was tested in a rabbit model of CM. ATI-2307 demonstrated significant fungicidal activity at dosages between 1 and 2 mg/kg/d, and these results were superior to fluconazole and similar to amphotericin B treatment. When ATI-2307 was combined with fluconazole, the antifungal effect was greater than either therapy alone. While ATI-2307 has potent anticryptococcal activity in the subarachnoid space, its ability to reduce yeasts in the brain parenchyma was relatively less over the same study period. This new drug, with its unique mechanism of fungicidal action and ability to positively interact with an azole, has demonstrated sufficient anticryptococcal potential in this experimental setting to be further evaluated in clinical studies.

Clinical Features of Cryptococcal Meningoencephalitis in HIV-Positive and -Negative Patients in a Resource-Limited Setting.

Cryptococcal meningoencephalitis is a systemic fungal infection in immunocompromised and immunocompetent individuals. This study investigated the clinical characteristics and factors associated with mortality in HIV-associated and non-HIV-associated cryptococcal meningoencephalitis in a resource-limited setting. This was a retrospective cohort study of patients with cryptococcal meningoencephalitis between January 2009 and December 2019 at a tertiary teaching hospital in Thailand. Overall, 1019 patients with cryptococcal meningoencephalitis were enrolled, and 923 (90.6%) were HIV-positive. The patients with HIV-associated cryptococcal meningoencephalitis were younger than the HIV-negative patients (37 versus 56 years, p < 0.01). The HIV-negative patients were more likely to have underlying conditions (52.1% versus 7.5%; p < 0.01), had a longer median duration of headaches prior to admission (14 days versus 6 days, p < 0.01), and were more likely to have an altered mental status at presentation (36.5% versus 18.6%, p < 0.01) and pulmonary involvement (15.6% versus 0.8%, p < 0.01). The HIV-positive patients had lower cerebrospinal fluid (CSF) white blood cell counts (4 versus 94 cells/mm3; p < 0.01), lower CSF protein (69 versus 157 mg/dL; p < 0.01), higher CSF glucose (38.8 versus 21 mg/dL; p < 0.01), and more frequent cryptococcemia (44.1% versus 20.5%; p < 0.01). The mortality rate was high but not significantly different between the two groups (30.2% versus 33.2%; p = 0.53). The HIV-positive patients with comorbidities, fever, an altered mental status at presentation, a CSF white blood cell count below 20 cell/mm3, fungemia, and positive CSF India ink were independently associated with 30-day mortality. In comparison, an altered mental status at presentation and fungemia were associated with 30-day mortality in HIV-negative patients. In conclusion, HIV-negative patients with cryptococcal meningoencephalitis had more extensive central nervous system inflammation, although the two groups' mortality rates were similar. Unfavorable prognostic factors included comorbidities, fever, an altered mental status at presentation, a low CSF white blood cell count, fungemia, and positive CSF India ink.

Immunization with a heat-killed prm1 deletion strain protects the host from Cryptococcus neoformans infection

ABSTRACT Systemic infection with Cryptococcus neoformans, a dangerous and contagious pathogen found throughout the world, frequently results in lethal cryptococcal pneumonia and meningoencephalitis, and no effective treatments and vaccination of cryptococcosis are available. Here, we describe Prm1, a novel regulator of C. neoformans virulence. C. neoformans prm1Δ cells exhibit extreme sensitivity to various environmental stress conditions. Furthermore, prm1Δ cells show deficiencies in the biosynthesis of chitosan and mannoprotein, which in turn result in impairment of cell wall integrity. Treatment of mice with heat-killed prm1Δ cells was found to facilitate the host immunological defence against infection with wild-type C. neoformans. Further investigation demonstrated that prm1Δ cells strongly promote pulmonary production of interferon-γ, leading to activation of macrophage M1 differentiation and inhibition of M2 polarization. Therefore, our findings suggest that C. neoformans Prm1 may be a viable target for the development of anti-cryptococcosis medications and, cells lacking Prm1 represent a promising candidate for a vaccine.

Cryptococcal meningoencephalitis: Risk factors associated to death in a hospital in Northeastern Brazil.

Cryptococcosis is an opportunistic systemic mycosis caused by pathogenic encapsulated yeasts of the genus Cryptococcus. The objective of the present study was to evaluate the risk factors associated with death of patients diagnosed with meningitis due to Cryptococcus spp. This retrospective cohort study included patients admitted to the São José Hospital (SJH) with Cryptococcal Meningoencephalitis (CM) who were diagnosed between 2010 and 2018. Data collection was carried out by reviewing the patients' medical records. Death during hospitalization was considered the primary outcome. From 2010 to 2018, 21,519 patients were admitted to the HSJ, 124 of whom were hospitalized due to CM. The CM incidence rate was 5.8 cases/103 hospitalizations. We included 112 patients in the study. Male patients were the most affected (82.1%), and the median age was 37 years [IQR: 29-45]. HIV coinfection occurred in 79.4% of the patients. Fever (65.2%) and headache (88.4%) were the most frequent symptoms. Greater cellularity in the CSF was the most related factor to CM in non-HIV individuals (p<0.05). Death during hospitalization occurred in 28.6% (n=32) of the patients. The independent risk factors associated with death during the hospitalization were women (p=0.009), age > 35 years (p=0.046), focal neurological deficits (p=0.013), altered mental status (p=0.018) and HIV infection (p=0.040). The twelve-month survival was lower in HIV-positive patients (p<0.05). Early diagnosis, optimal treatment, and clinical follow-up strategies, especially in HIV patients, should be prioritized.

Cryptococcal meningoencephalitis with Actinomyces odontolyticus sepsis: a case report and literature review

BackgroundThe combined infection of actinomyces odontolyticus sepsis and cryptococcal encephalitis is rare in routine clinical practice. Thus, we presented this case report and literature review to provide clues to improve such patients' diagnoses and treatment processes.Case presentationThe main clinical manifestations of the patient were high fever and intracranial hypertension. Then, we completed the routine cerebrospinal fluid examination, biochemical detection, cytological examination, bacterial culture, and India ink staining. Firstly, the blood culture suggested actinomyces odontolyticus infection, considering the possibility of actinomyces odontolyticus sepsis and intracranial actinomyces odontolyticus infection. Accordingly, the patient was administered penicillin for treatment. Although the fever was slightly relieved, the symptoms of intracranial hypertension did not relieve. After 7 days, the characteristics of brain magnetic resonance imaging and the results of pathogenic metagenomics sequencing and cryptococcal capsular polysaccharide antigen suggested that cryptococcal infection. Based on the above results, the patient was diagnosed with a combined infection of cryptococcal meningoencephalitis and actinomyces odontolyticus sepsis. Anti-infection therapy with ‘penicillin, amphotericin, and fluconazole’ was provided, improving the clinical manifestations and objective indexes.ConclusionThe combined infection of Actinomyces odontolyticus sepsis and cryptococcal encephalitis is first reported in this case report, and combined antibiotics with ‘penicillin, amphotericin, and fluconazole’ are effective.

Cryptococcal Meningoencephalitis in HIV/AIDS Patient Coinfected with Tuberculosis. Case Report

Cryptococcal meningitis is an inflammation of the meninges due to Cryptococcus fungal infection which commonly invades people living with immunodeficiency virus (PLHIV) with impaired immunity. The disease has a high mortality rate and is frequently misdiagnosed in the early stages due to vague symptoms. This case report aimed to provide information regarding the diagnosis and management of cryptococcal meningoencephalitis in patients with acquired immunodeficiency syndrome (AIDS) and tuberculosis. We reported a case of a 34-year-old woman that complained of headache and fever for the last month. There were also oral white patches in the last two weeks. The patient was diagnosed with lung tuberculosis (TB) and human immunodeficiency virus (HIV) in February 2021, but the TB was just being treated in the last two months, and HIV in the last two weeks.

Persistent neurological symptoms and elevated intracranial pressures in a previously healthy host with cryptococcal meningitis

Cryptococcal meningoencephalitis can occur in both previously healthy and immunocompromised hosts. Here, we describe a 55 year-old HIV-negative male with no known prior medical problems, who presented with three months of worsening headaches, confusion, and memory changes without fever. Magnetic resonance imaging of the brain demonstrated bilateral enlargement/enhancement of the choroid plexi, with hydrocephalus, temporal and occipital horn entrapments, as well as marked periventricular transependymal cerebrospinal fluid (CSF) seepage. CSF analysis yielded a lymphocytic pleocytosis and cryptococcal antigen titer of 1:160 but sterile fungal cultures. Despite standard antifungal therapy and CSF drainage, the patient had worsening confusion and persistently elevated intracranial pressures. External ventricular drainage led to improved mental status but only with valve settings at negative values. Ventriculoperitoneal shunt placement could thus not be considered due to a requirement for drainage into the positive pressure venous system. Due to this persistent CSF inflammation and cerebral circulation obstruction, the patient required transfer to the National Institute of Health. He was treated for cryptococcal post-infectious inflammatory response syndrome with pulse-taper corticosteroid therapy, with resultant reductions in CSF pressures along with decreased protein and obstructive material, allowing successful shunt placement. After tapering of corticosteroids, the patient recovered without sequelae. This case highlights (1) the necessity to consider cryptococcal meningitis as a rare cause of neurological deterioration in the absence of fever even in apparently immunocompetent individuals and (2) the potential for obstructive phenomena from inflammatory sequelae and the prompt response to corticosteroid therapy.

Cryptococcal meningoencephalitis in an immunodeficiency virus positive patient coinfected with tuberculosis

Background: Cryptococcal meningitis is an inflammation of the meninges due to Cryptococcus fungal infection which commonly invades people living with immunodeficiency virus (PLHIV) with impaired immunity. The disease has a high mortality rate and is frequently misdiagnosed in the early stages due to vague symptoms. This case report aimed to provide information regarding diagnosing and managing cryptococcal meningoencephalitis in patients with acquired immunodeficiency syndrome (AIDS) and tuberculosis. Case presentation: We reported a case of 34-year-old woman that complained of headache and fever from one month ago. There were also oral white patches in the last two weeks. The patient was diagnosed with lung TB and human immunodeficiency virus (HIV) in February 2021, but the TB was just being treated in the past two months and HIV in last two weeks. Head CT-scan with contrast showed meningoencephalitis, brain edema, left frontal, left ethmoidal, left and right maxillary and left sphenoid sinusitis. On the 9th day of hospitalization, the patient had seizures. Analysis of the cerebrospinal fluid culture revealed Cryptococcus neoformans. The patient’s comorbidities were leucopenia, hypoalbuminemia, pneumonia, brain edema which led to poor prognosis. On the 10th day, the seizures relapsed, followed by the drastically reduced SpO2 and death. Septic shock and multiorgan failure were considered the cause of the case's death. Conclusion: This case highlights the importance of early diagnosis and management to avoid unfavorable outcome.

Successful Treatment with High-Dose Immunoglobulin of a Complicated Patient with Catatonia and Central Nervous System Autoantibodies

Ms. X is a 52-year-old Filipino female with no prior psychiatric or medical history who initially presented to an outside hospital for new onset headache, neck pain, and altered mental status. She was admitted inpatient medicine service and was found to have HIV/AIDs and cryptococcal meningoencephalitis. Ms. X had a good response to appropriate antifungal therapies and was able to discharge home with full resolution of symptoms on high dose fluconozaole. Unfortunately, Ms. X developed transaminitis on high dose fluconazole, the dose was reduced and she presented to our institution with recurrent cryptococcal meningoencephalitis as evidenced by elevated titers of cryptococcal antigen in CSF and MRI studies showing T2 and FLAIR hyperintensities in bilateral basal ganglia, thalamus and medial temporal lobes and evidence of intracranial hypertension. Consequently, Ms. X developed prominent neuropsychiatric symptoms including agitation, cognitive impairment, paranoia, visual hallucinations and symptoms of catatonia. Despite adequate treatment of the cryptococcal infection evidenced by decreasing cryptococcal antigen titers in CSF, and appropriate psychiatric treatment, her neuropsychiatric symptoms persisted and her MRI studies continued to show signs of neuroinflammation in the aforementioned areas. Antibody testing for basal ganglia targets was completed to investigate a possible non-infectious cause of neuroinflammation and neuropsychiatric symptoms. Ms. X was found to have elevated titers of anti-D1, anti-GM1 and anti-tubulin receptor antibodies in her CSF. Due to the severity and treatment resistant nature of her neuropsychiatric symptoms, she was treated with 2 g/kg/day IVIG for 4 days. She showed significant improvement in her neuropsychiatric symptoms after 3 days and full resolution of her neuropsychiatric symptoms 1 week following IVIG. Given remarkable clinical response to IVIG a second round of IVIG was administered 2 weeks later in order to sustain the response. After several months of prolonged hospitalization, Ms X was able to discharge to the care of her family and to date her neuropsychiatric symptoms remain in remission. We propose Ms. X’s persistent, treatment resistant neuropsychiatric symptoms were related to a post-infectious inflammatory encephalopathy that responded robustly to IVIG.

Cryptococcal Meningoencephalitis and Immune Reconstitution Inflammatory Syndrome in a patient on Tocilizumab Therapy: A Case Report (P1-10.005)

<h3>Objective:</h3> To describe a case of cryptococcal meningoencephalitis complicated by immune reconstitution inflammatory syndrome (IRIS), vasculitis, ischemic strokes, and hydrocephalus. <h3>Background:</h3> Cryptococcus neoformans is the most common cause of fungal meningitis worldwide and typically affects individuals with defects in cell-mediated immunity. A 71-year-old female with giant cell arteritis on daily prednisone and monthly Tocilizumab infusions presented with worsening headaches for 2 weeks and new-onset confusion for 3 days. Initial workup revealed hyponatremia (sodium 125 mmol/L) and community acquired pneumonia. She was treated with antibiotics, but her mental status rapidly declined necessitating endotracheal intubation. MRI Brain demonstrated multifocal areas of diffusion restriction in the bilateral cerebral and cerebellar hemispheres, basal ganglia, and brainstem with diffuse leptomeningeal enhancement. Cerebrospinal fluid (CSF) studies revealed an elevated opening pressure of 28 cm H₂O, positive CSF cryptococcal antigen, and CSF fungal cultures grew cryptococcus neoformans. She was started on empiric liposomal amphotericin B and flucytosine before the cryptococcal antigen and cultures resulted. Despite treatment, her neurological status continued to decline with repeat MRI showing new ischemic infarctions, subarachnoid hemorrhages, and leptomeningeal and parenchymal enhancement. Digital subtraction angiography revealed cerebral vasospasm and possible vasculitis. Repeat lumbar puncture demonstrated persistently elevated opening pressure, continued pleocytosis, and increased protein. She was continued on antifungal therapy and received IV methylprednisolone for IRIS. She additionally underwent ventriculoperitoneal (VP) shunt placement. Despite these interventions, her clinical status continued to deteriorate and she was palliatively extubated. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> N/A <h3>Conclusions:</h3> This patient presented with cryptococcal meningoencephalitis in the setting of immune suppression from prednisone and tocilizumab, a monoclonal antibody that targets the IL-6 receptor. Despite early and appropriate treatment, she continued to worsen with multiple complications including IRIS, a dysfunctional inflammatory response to infection precipitated by immune recovery. In patients treated appropriately for cryptococcal meningoencephalitis, a failure to respond should raise concern for complicating conditions. <b>Disclosure:</b> Dr. Navalkar has nothing to disclose. Dr. Sui has nothing to disclose. The institution of Dr. Bashir has received research support from NIH. The institution of Dr. Bashir has received research support from PICORI. The institution of Dr. Bashir has received research support from Sanofi. Dr. Bashir has received research support from GWSP. The institution of Dr. Bashir has received research support from Roche. The institution of Dr. Bashir has received research support from Novartis. The institution of Dr. Bashir has received research support from Hoffmann-La Roche.