Post covid cerebral phaeohyphomycosis by Rhinocladiella mackenziei: An unusual association.

Cerebral phaeohyphomycosis (CP) is a rare but a highly morbid fungal infection of the central nervous system caused by the fungi belonging to the order Chaetothyriales, which includes Cladophialophora bantiana, Exophiala dermatitidis, Rhinocladiella mackenziei (RM) etc. This disease is associated with poor clinical outcomes, with reported mortality of over 80%. We present the case of a 65-year gentleman who developed CP secondary to RM infection following COVID-19 and the associated challenges in his medical and surgical management.

First case of Rhinocladiella mackenziei brain abscess in Turkey: Case report and review of the literature.

Rhinocladiella mackenziei is a highly neurotropic fungus, mainly reported from the Middle East. However, in recent years, there have been some cases from outside this region. We described an additional fatal case of R. mackenziei cerebral infection for the first time from Turkey and made a literature review of all previously reported cases. During 34 years (1988-2022), there have been 42 R. mackenziei brain abscess cases. Most patients have been reported from Saudi Arabia (n = 14, 33.3%). It is noteworthy that 40.5% of patients, including our case, were immunocompetent at initial diagnosis and mostly presented with a single lesion (n = 10, 23.8%). The most frequent comorbidities were solid organ transplant (n = 9, 21.4%), diabetes mellitus (n = 6, 14.3%), malignancy (n = 6, 14.3%) and prior surgery (n = 3, 7.1%). The most commonly used initial antifungal regimen were amphotericin B together with itraconazole (n = 9, 21.4%), combinations of lipid preparations of amphotericin B, voriconazole and/or posaconazole (n = 9, 21.4%) and amphotericin B alone (n = 8, 19%). Although both surgical procedures and antifungal medication in the majority of patients were performed, mortality rates remained high (90.4%). The area at risk of R. mackenziei cerebral abscess cases extends to other countries. Clinicians should be aware of this emerging disease and take a detailed travel history in patients with atypical and undocumented brain abscesses. Our case confirms the hypothesis that this fungus might spread more widely than previously predicted regions.

The Impact of Paracoccidioides spp Infection on Central Nervous System Cell Junctional Complexes.

Paracoccidioidomycosis (PCM), a systemic mycosis caused by the fungus Paracoccidioides spp. is the most prevalent fungal infection among immunocompetent patients in Latin America. The estimated frequency of central nervous system (CNS) involvement among the human immunodeficiency virus (HIV)/PCM-positive population is 2.5%. We aimed to address the impact of neuroparacoccidioidomycosis (NPCM) and HIV/NPCM co-infection on the tight junctions (TJ) and adherens junction (AJ) proteins of the CNS. Four CNS formalin-fixed paraffin-embedded (FFPE) tissue specimens were studied: NPCM, NPCM/HIV co-infection, HIV-positive without opportunistic CNS infection, and normal brain autopsy (negative control). Immunohistochemistry was used to analyze the endothelial cells and astrocytes expressions of TJ markers: claudins (CLDN)-1, -3, -5 and occludin; AJ markers: ß-catenin and E-cadherin; and pericyte marker: alpha-smooth muscle actin. FFPE CNS tissue specimens were analyzed using the immunoperoxidase assay. CLDN-5 expression in the capillaries of the HIV/NPCM coinfected tissues (mixed clinical form of PCM) was lower than that in the capillaries of the HIV or NPCM monoinfected (chronic clinical form of PCM) tissues. A marked decrease in CLDN-5 expression and a compensatory increase in CLDN-1 expression in the NPCM/HIV co-infection tissue samples was observed. The authors suggest that Paracoccidioides spp. crosses the blood-brain barrier through paracellular pathway, owing to the alteration in the CLDN expression, or inside the macrophages (Trojan horse).

[Pathogenic spectrum and laboratory indicators of fungal infections in the central nervous system].

Central nervous system (CNS) fungal infections are challenging and difficult to diagnose and treat. This article introduces the high risk factors, pathogen spectrum and laboratory indicators that cause CNS fungal infection. As patients with CNS fungal infections are often accompanied by immunodeficiency, it is especially necessary for clinical early detection, early prevention, and early diagnosis, and timely and effective implementation of optimized diagnosis and treatment programs to prevent further deterioration of the disease.

Pathogenic spectrum and laboratory indicators of fungal infections in the central nervous system / 中华预防医学杂志

Central nervous system (CNS) fungal infections are challenging and difficult to diagnose and treat. This article introduces the high risk factors, pathogen spectrum and laboratory indicators that cause CNS fungal infection. As patients with CNS fungal infections are often accompanied by immunodeficiency, it is especially necessary for clinical early detection, early prevention, and early diagnosis, and timely and effective implementation of optimized diagnosis and treatment programs to prevent further deterioration of the disease.

CT and MRI Findings of Invasive Mucormycosis in the Setting of COVID-19: Experience From a Single Center in India.

An increasing incidence of rhinoorbitocerebral mucormycosis (ROCM) among patients with COVID-19 has recently been reported in India. We report the imaging findings for 25 patients with COVID-19 and invasive ROCM at a single hospital in India. Findings included sinus wall erosions (n = 20), air within bony sinus structures (n = 11), and focal mucosal nonenhancement (n = 8). Orbital, vascular, and intracranial complications were also observed. Radiologists should recognize the increasing incidence of ROCM among patients with COVID-19 to facilitate early diagnosis.

Neuroradiology of infectious diseases.

PURPOSE OF REVIEW: Early diagnosis of central nervous system (CNS) infections is crucial given high morbidity and mortality. Neuroimaging in CNS infections is widely used to aid in the diagnosis, treatment and to assess the response to antibiotic and neurosurgical interventions. RECENT FINDINGS: The Infectious Diseases Society of America (IDSA) guidelines have clear recommendations for obtaining a computerized tomography of the head (CTH) prior to lumbar puncture (LP) in suspected meningitis. In the absence of indications for imaging or in aseptic meningitis, cranial imaging is of low utility. In contrast, cranial imaging is of utmost importance in the setting of encephalitis, bacterial meningitis, ventriculitis, bacterial brain abscess, subdural empyema, epidural abscess, neurobrucellosis, neurocysticercosis, and CNS tuberculosis that can aid clinicians with the differential diagnosis, source of infection (e.g., otitis, sinusitis), assessing complications of meningitis (e.g., hydrocephalus, venous sinus thrombosis, strokes), need for neurosurgical interventions and to monitor for the response of therapy. Novel imaging techniques such as fast imaging employing steady-state acquisition (FIESTA), susceptibility-weighted imaging (SWI), and chemical exchange saturation transfer (CEST) contrast are briefly discussed. SUMMARY: Though the radiological findings in CNS infections are vast, certain patterns along with clinical clues from history and examination often pave the way to early diagnosis. This review reiterates the importance of obtaining cranial imaging when necessary, and the various radiological presentations of commonly encountered CNS infections.

Central nervous system infections after solid organ transplantation.

PURPOSE OF REVIEW: Significant advances to our understanding of several neuroinfectious complications after a solid organ transplant (SOT) have occurred in the last few years. Here, we review the central nervous system (CNS) infections that are relevant to SOT via a syndromic approach with a particular emphasis on recent updates in the field. RECENT FINDINGS: A few key studies have advanced our understanding of the epidemiology and clinical characteristics of several CNS infections in SOT recipients. Risk factors for poor prognosis and protective effects of standard posttransplant prophylactic strategies have been better elucidated. Newer diagnostic modalities which have broad clinical applications like metagenomic next-generation sequencing, as well as those that help us better understand esoteric concepts of disease pathogenesis have been studied. Finally, several studies have provided newer insights into the treatment of these diseases. SUMMARY: Recent findings reflect the steady progress in our understanding of CNS infections post SOT. They provide several avenues for improvement in the prevention, early recognition, and therapeutic outcomes of these diseases.

Central Nervous System Histoplasma-Associated Post-infectious Inflammatory Response Syndrome (Histo-PIIRS).

We present a case of central nervous system (CNS) histoplasmosis in a previously healthy adult with hepatitis C (HCV) presenting with neurological symptoms refractory to antifungal therapy and ventriculoperitoneal (VP) shunting 4 months after initial diagnosis. Persistent symptoms were thought to be inflammatory rather than infectious given negative cerebrospinal fluid (CSF) and serum fungal antigens. The patient promptly improved after initiation of corticosteroid therapy. Elevated CSF cytokines and regional enhancement on brain MRI resolved with corticosteroid treatment. This is the first case of Histoplasma-associated post-infectious inflammatory response syndrome (Histo-PIIRS) documented by CSF cytokine reduction in response to corticosteroid therapy.

Central nervous system candidiasis beyond neonates: Lessons from a nationwide study.

Though candidiasis is the most frequent invasive fungal infection, Candida spp. central nervous system (CNS) infections are rare but severe. To further describe clinico-patho-radiological presentations of this entity, we report a retrospective study from January 2005 to December 2018 including patients aged ≥ 28 days with proven or probable CNS candidiasis in France. Twenty-four patients were included. Seventeen patients (70%) had CNS localization secondary to disseminated candidiasis (10 with hematologic malignancies [HM]; the seven other patients had infective endocarditis [IE]). Among patients with HM, seven previously had lumbar puncture for intrathecal chemotherapy, the three others had IE. Among patients with disseminated infection, magnetic resonance imaging (MRI) evidenced meningitis (17%), micro-abscesses (58%), or vascular complications (67%). Seven patients (30%) had isolated CNS involvement related to neurosurgery (n = 2), CARD9 deficiency (n = 2), intravenous drug use, diabetes mellitus, or no identified predisposing condition (n = 1 each). All evaluated patients with isolated CNS involvement had meningitis on cerebrospinal fluid (CSF) and intracranial hypertension. For the latter patients, MRI evidenced meningitis (71%) or abscesses (57%). Among all patients, cerebrospinal fluid (CSF) culture grew Candida spp. in 31% of cases. CSF ßDGlucan or mannan Ag were positive in respectively 86% and 80% of cases. Mortality attributed to CNS candidiasis was 42%: 53% in case of disseminated infection (70% for HM) and 14% in case of localized infection. CNS candidiasis are isolated or occur during disseminated infection in patients with HM and lumbar puncture for intrathecal chemotherapy or during IE. Clinical, radiological finding and outcome highly vary according to CNS localized versus disseminated candidiasis. LAY SUMMARY: Candida is a yeast and is the most common cause of fungal infections worldwide. Candida central nervous system (CNS) infections are rare, severe, and poorly described. We report a retrospective study from January 2005 to December 2018 including patients aged ≥ 28 days with proven or probable CNS candidiasis in France. Twenty-four patients were included (14 men, median age 51 years). Seventeen patients had CNS localization secondary to disseminated candidiasis from blood to CNS (10 with hematologic malignancies [HM], the seven other patients had infective endocarditis [IE]). Seven patients had isolated CNS involvement related to neurosurgery (n = 2), CARD9 deficiency (n = 2), intravenous drug use (n = 1), diabetes mellitus (n = 1), or no identified risk factor (n = 1).During Candida CNS infections, brain lesions were meningitis abscesses or vascular complications. Cerebrospinal fluid (CSF) culture grew Candida spp. in 31% of cases. Forty-two percent of patients died from infection: 53% in case of disseminated infection (70% for HM) and 14% in case of localized infection.

Cryptococcosis caused by cryptococcus gattii: 2 case reports and literature review.

Cryptococcosis caused by Cryptococcus gattii, is a life threatening fungal infection with recently increasing prevalence. C. gattii is a species complex comprising multiple independent species. However, many biological characteristics and clinical features of cryptococcosis due to C. gattii are relatively less well defined. In this paper, we identify two cases of C. gattii infection, and laboratory findings of genotype VGI and VGII in two groups of apparently immunocompetent Chinese individuals respectively. Upon detailed review of all 35 cases of C. gattii infections, it was observed that C. gattii can cause debilitating illness in both immunocompetent and immunocompromised individuals. Cryptococcosis due to C. gattii is a serious systemic fungal infection, with pulmonary central nervous system tropism. Epidemiologically, C. gattii infection is not only restricted in tropical and subtropical regions, but also in other geographical settings.

Isolated cerebral mucormycosis associated with intravenous drug use.

We present an uncommon case of isolated basal ganglia mucormycosis in a patient without any known cause of immunosuppression, but with a history of drug injection. The patient presented a good clinical and radiological response to antifungal treatment without aggressive surgical debridement (liposomal amphotericin B combined with isavuconazole for 4 weeks followed by isavuconazole as maintenance therapy for 10 months).

Invasive rhino-orbital-cerebral aspergillosis in an immunocompetent patient.

INTRODUCTION: Rhino-orbital-aspergillosis (ROA) is a rare but serious disease in immunocompetent patients. Diagnosis is often delayed due to the absence of specific clinical symptoms. We describe the case of a patient who presented initially with ROA which spread progressively to the right ethmoid-sphenoid sinuses and then to the brain. OBSERVATION: A 61-year-old patient with a history of well-controlled diabetes presented with a sudden severe decrease in right visual acuity. Cerebral MRI showed the presence of an infiltrate in the right orbital apex extending to the homolateral cavernous sinus without any cerebral involvement. A diagnosis of right orbital myositis was made and corticosteroid therapy was started. His symptoms worsened progressively leading to quasi-blindness. A new MRI showed the development of right sphenoid-ethmoid osteolytic lesions. A fungal aetiology was suspected and tests for fungal biomarkers found a ß-(1-3)-D-glucan level of 99pg/ml but negative galactomannan. An ethmoid biopsy was performed for histological and mycological investigations, including the detection of Aspergillus DNA by qPCR. qPCR was positive and culture resulted in the isolation of multi-sensitive Aspergillus fumigatus. Treatment was initiated with voriconazole. Due to persistence of blindness and the appearance of a lesion extending to the right frontal lobe, surgical excision was performed followed by antifungal treatment for a total duration of 1year. The patient is currently stable, but has persistence of blindness in the right eye. CONCLUSION: Invasive ROA is a rare but serious disease in immunocompetent patients which should be evoked in the differential diagnosis of a tumour or vasculitis. Early diagnosis is essential for optimal management.

Disseminated histoplasmosis presenting as bilateral lower extremity paresis.

Histoplasmosis is the most common endemic mycosis in the United States and is caused by the organism Histoplasma capsulatum. Infection is often asymptomatic or self-limited, but when symptomatic it usually presents in the form of pulmonary histoplasmosis. In its most severe form, H. capsulatum can spread to extrapulmonary sites causing disseminated infection. Here we present a peculiar case of central nervous system (CNS) histoplasmosis wherein multiple focal spinal cord lesions were the only manifestation of CNS infection, causing bilateral lower extremity paresis and loss of sensation. Although uncommon, CNS histoplasmosis should be included in the differential diagnosis when a patient presents with meningitis, encephalitis, or isolated brain or spinal cord lesions in endemic areas.

Central Nervous System Fungal Infection-Related Stroke: A Descriptive Study of Mold and Yeast-Associated Ischemic Stroke.

OBJECTIVE: Central nervous system (CNS) ischemic events caused by fungal infections are rare, and clinical characteristics of these ischemic events are largely unknown. The objective of this manuscript is to highlight characteristics of fungal-related strokes and describe possible mechanistic differences between CNS mold and yeast infection-related strokes. METHODS: We report a single-center retrospective case series of all adult patients who presented with concurrent CNS fungal infection and stroke between 2010 and 2018. Patients believed to have a stroke etiology due to cardioembolic, atheroembolic, or strokes nontemporally associated with a CNS fungal infection and those with incomplete stroke workups were excluded from analysis. RESULTS: Fourteen patients were identified with ischemic stroke and concurrent CNS fungal infection without other known ischemic stroke etiology. Eight patients had a CNS yeast infection, and 6 had a CNS mold infection. All patients presented with recurrent or progressive stroke symptoms. Six patients were immune-compromised. Four patients admitted to intravenous drug use. All yeast infections were identified by cerebrospinal fluid culture or immunologic studies while all but one of the mold infections required identification by tissue biopsy. Leptomeningeal enhancement was only associated with CNS yeast infections, while basal ganglia stroke was only associated with CNS mold infections. CONCLUSION: Ischemic stroke secondary to CNS fungal infections should be considered in patients with recurrent or progressive cryptogenic stroke, regardless of immune status and cerebrospinal fluid profile. CNS yeast and mold infections have slightly different stroke and laboratory characteristics and should have a distinct diagnostic method. Depending on clinical suspicion, a thorough diagnostic approach including spinal fluid analysis and biopsy should be considered.

Cerebral phaeohyphomycosis due to Cladophialophora bantiana in a French Guianese child.

We report a case of cerebral phaeohyphomycosis, a fungal brain infection due to a dark (dematiaceous) fungi in a 6-year-old French Guyanese boy. The child presented fever and drowsiness due to several paraventricular brain abscesses. Neurological surgeries were performed to reduce intracranial hypertension and to obtain abscess biopsies. Mycological cultures of intraoperative samples led to the diagnosis of cerebral phaeohyphomycosis due to Cladophialophora bantiana. The patient neurological status deteriorated and remained critical after several weeks of combination antifungal therapy with voriconazole 8mg/kg/day, liposomal amphotericin B 10mg/kg/day and flucytosine 200mg/kg/day. A complete surgical resection was not possible because of multiple small abscesses. A multidisciplinary ethical staff decided on home medical care with palliative ventriculoperitoneal shunt, nasogastric feeding and analgesics. One year later, the patient's neurological condition had improved and cerebral lesions had regressed, while he had not received any antifungal treatment but only traditional medicines. Cerebral phaeohyphomycosis are rare diseases affecting immunocompromised but also apparently non-immunocompromised patients, as in this case. A complete surgical resection is not always possible and mortality rates are high in spite of treatments with a combination of antifungals. The diagnosis may be difficult because of these dematiaceous fungi's slowly growing and their potential pathogenicity for laboratory staff.