Fungal Infections Of Central Nervous System Research Articles

A Study of the Etiology, Clinical Profile, and Diagnosis of Various Types of Central Nervous System Infections in a Tertiary Care Center.

Introduction Infections affecting the central nervous system (CNS) can stem from various sources, including bacteria, viruses, and fungi, manifesting as conditions like meningitis, encephalitis, meningoencephalitis, and brain abscesses. Despite significant advancements in diagnosis and treatment, these infections continue to pose substantial risks to life. Several factors contribute to the causes of CNS infections. Demographic and geographic elements, the health status of individuals, their immune system's strength, the availability of diagnostic tools, and local prevention initiatives, all play pivotal roles. Consequently, the necessity of comprehensive local epidemiological data becomes undeniable as it guides the need for further studies and research. Understanding these factors is crucial for enhancing preventive measures and optimizing treatment strategies in tackling CNS infections. Aims and objectives This research aims to study the etiology and clinical features of different CNS infections among hospitalized patients and to diagnose cases of CNS infections based on laboratory and radiological investigations. Material and methods One hundred adults, seeking treatment for neurological impairments at a specialized tertiary care center in Gujarat, India, volunteered for this cross-sectional observational research. The study investigated the etiology, clinical profiles, and diagnoses of different CNS infections. It delved into the prevalence of these infections across age and sex categorieswhile also observing mortality rates. Results In our research, we observed that bacterial causes were the most prevalent among CNS infections. Tubercular meningitis accounted for 36%, tuberculoma 14%, and pyogenic bacterial infections 23%. Following this, fungal infections emerged as the second most frequent, with mucormycosis at 9% and cryptococcus at 1%. Other less common CNS infections included viral encephalitis (4%), neurocysticercosis (3%), and brain abscess (1%). Middle-aged individuals between 41 and 60 years were most commonly affected (43%), followed by those aged 21-40 years (31%). Males accounted for a higher percentage of cases at 58%. Clinical symptoms revealed fever as the predominant feature (80%), with headaches following closely at 67%. Acute presentations were prevalent, representing 83% of cases, while neck stiffness was noted in 62% of patients. Most patients exhibited normal hemoglobin levels (96%) and a majority had a normal total leukocyte count (79%). Notably, 31% of the studied patients were identified as People Living With HIV (PLHIV). Out of 100 patients, 79 survived with appropriate treatment, resulting in a mortalityof 21%. Conclusion The study identified various CNS infections, including bacterial (acute pyogenic meningitis, tubercular meningitis, tuberculoma, brain abscesses, and neurosyphilis), viral (viral meningitis and encephalitis), fungal (cryptococcal meningitis and CNS mucormycosis), and parasitic infections (neurocysticercosis and CNS toxoplasmosis). Tuberculous meningitis emerged as the most prevalent, followed by pyogenic meningitis. Clinical symptoms predominantly featured fever, headache, and altered sensorium, with less common occurrences of seizures, vomiting, weakness, and speech disturbances. Elevated CSFproteins and total leukocyte count were common findings in CSF analysiswhile consistent radiological observations included hypodensities in brain tissue and leptomeningeal enhancement.

CNS Fungal Infections in Liver Transplantation

Context: Liver transplant recipients are highly susceptible to infections, including those affecting the central nervous system (CNS), due to their compromised immune systems and underlying chronic comorbidities. Results: Despite recent advancements in diagnostic and treatment modalities, post-transplant fungal infections continue to affect these patients. CNS fungal infections following liver transplantation pose a significant challenge in the diagnostic and therapeutic management of transplant recipients. Timely diagnosis and treatment are crucial because these infections are often identified late, leading to substantial morbidity and mortality in this patient population. Conclusions: This mini-review aims to explore the incidence of CNS fungal infections in liver transplant recipients, the key opportunistic pathogens involved, the associated risk factors, various clinical presentations, and the importance of preventive measures.

The Risk of Infections in Adults with Primary Immune Thrombocytopenia (ITP)

Background Immunosuppressive treatment has remained a cornerstone in the management of primary ITP (pITP) for decades. Infections are known complications to immunosuppressive therapy, but the actual risk is not well studied in ITP. We have previously shown that the overall mortality risk is increased in pITP patients and specifically that death due to infections is 1.5-2.4-fold elevated compared to the general population. In this study,we aimed at quantifying the risk of infection, including infection subtypes, in adults with pITP and matched comparators from the general population. Study design We constructed a nationwide cohort of patients ≥18 years with pITP using the Danish Civil Registration System (CRS) and the Danish National Patient Registry (DNPR). We identified ITP patients using the specific ICD-10 diagnosis registration and age-sex matched these with up to 40 comparators without ITP from the general population. We excluded prevalent ITP, non-ITP thrombocytopenic disorders, and secondary ITP defined as one or more associated diagnosis registered any time before or up to 30 days after diagnosis of ITP. The latter included ITP in combination with hematological malignancies, autoimmune disorders etc. Hospital registered infections were identified through the DNPR, prior to 1995 using ICD-8 and ICD-10 diagnoses codes thereafter. Diagnosis codes were grouped, defining the following seven types or sites of infection: respiratory, urogenital, bloodstream, gastrointestinal, tissue and musculoskeletal, central nervous system (CNS), candidiasis and other fungal infections. Date of first registration of pITP marked start of follow-up and comparators were assigned the same start date. Patients and comparators were followed to the first of following events in each of the seven subgroups: infection, emigration, death, or end of study period (31 st of December 2016). Infections occurring before start date were categorized as prevalent. We computed 1-year, 5-year, and 10-year as well as overall cumulative incidences. In addition, relative increases in risk were estimated using Cox-specific hazard (csHR) and Fine-Gray subhazard ratios (subHR) with and without equivalent time-splits, and death as competing event. Results We identified 4,030 pITP patients and 161,020 matched comparators. In the combined group of all types of infections total follow-up time was 22,075 person-years (average 5.5 years) for pITP patients and 1,118,304 person-years (average 6.9 years) for comparators. Median age was 60 years [IQR 40-74]. Previous hospital registered infections had occurred in 37% of patients and 27% of comparators. Comorbidity was more frequent among pITP patients than among comparators. The 1-year cumulative incidences in all subgroups of infections were higher in patients compared with the general population (Figure 1). For blood stream infections the 1-year cumulative incidence reached 3.36% [95% CI 2.83-3.96] in patients and 0.47% [95% CI 0.44-0.51] in comparators. The cumulative incidences for all subtypes of infections remained higher for patients than comparators throughout the study period, but differences decreased over time. During the first year adjusted csHR for infections overall was 2.82 [95%CI 2.61-3.05] and the adjusted subHR was 2.20 [95% CI 2.01-2.41]. Blood stream infections had the relative highest risk with an adjusted csHR of 6.58 [95% CI 5.46-7.92] and adjusted subHR of 2.08 [95% CI 1.71-2.54] (Figure 2). Risks of the other types of infections were also increased during first year but diminished over time in general (Figure 2). For the entire study period the overall adjusted csHR of all infections was 1.51 [95% CI 1.35-1.67] with a subHR of 1.34 [95% CI 1.20-1.49]. Blood stream infections continued having the highest risk in the period between 6 th-10 th year with a csHR of 1.40 [95% CI 1.03-1.91]. Conclusion The risk of incident infection in patients with pITP is increased compared with the general population. This risk is especially elevated within the first year after diagnosis but remains higher than the general population also in subsequent years. The risk of blood stream infection is especially high within the first year after diagnosis, but remains higher even 20 years after diagnosis. These data may help clinicians to improve management of ITP and support shared decision making with patients.

Central Nervous System Fungal Infections, Diagnostics, and Antifungals: Is There “Mush-room” for Improvement?

The blood brain barrier (BBB) controls the passage of molecules between the circulatory system and the central nervous system. Despite this, some fungi find ways to bypass the BBB, resulting in infections of the central nervous system (CNS) including meningitis, meningoencephalitis, and abscesses. While these infections are rare, the resultant mortality rates range from 30 to 99%, in part due to the poor penetration of most commercially available antifungals. Additionally, laboratory diagnostics can lack sensitivity and/or specificity and may require specialized diagnostic testing facilities, also contributing to the high mortality rate seen in CNS mycoses. Despite the high risk of mortality, detailed understanding of how these infections occur is limited to only a few of the most common fungi, and there is a dearth of research examining novel therapies to aid in the treatment of these infections.

Invasive Fungal Infection of the Duramater as the Presenting Manifestation of Disseminated Sarcoidosis (P10-10.005)

<h3>Objective:</h3> To describe a case of invasive fungal infection of the duramater which was the presenting manifestation of Disseminated sarcoidosis <h3>Background:</h3> Invasive Central nervous system fungal infections are usually encountered in the setting of immunosuppressive conditions, craniospinal trauma or instrumentation. It is rare for a treatment naïve patient with sarcoidosis to develop fungal infection of the duramater. <h3>Design/Methods:</h3> We describe the case of a young male who was found to have nodular thickening of the duramater due to Invasive CNS fungal infection. <h3>Results:</h3> We had a 27 year old man who had no prior comorbidities who presented with a single seizure. On evaluation, he was found to have nodular thickening of the Duramater. Differentials of infective, inflammatory, histiocytic and malignant conditions were considered. He underwent detailed evaluation and PET-CT revealed generalized lymphadenopathy. Biopsy from the dural thickening revealed septate hyphae and fungal culture showed Acremonium species. There were granulomas found on histopathologic examination of the dural as well as subcarinal lymphnode biopsy. He was treated with Voriconazole for 24 weeks followed by treatment of sarcoidosis. <h3>Conclusions:</h3> Sarcoidosis may be associated with immunodeficiency due to its effects on the lymphocytes, bone marrow and other organs such as the thymus. There have been several reports of patients with sarcoidosis being predisposed to infections such as Progressive multifocal leukoencephalopathy, fungal infections, tuberculosis and other bacterial infections. These infections may occur de-novo in the absence of immunosuppressant drugs or corticosteroids which have been traditionally used in the management of sarcoidosis with organ threatening or life threatening symptoms. Infections that occur as the first manifestation of an underlying autoimmune condition are challenging to diagnose. Appropriate diagnosis is essential to ensure optimum treatment of both conditions. <b>Disclosure:</b> Dr. Elavarasi has stock in Pfizer. Dr. Elavarasi has stock in PGHL. The institution of Dr. Elavarasi has received research support from All India Institute of Medical Sciences, New Delhi. The institution of Dr. Elavarasi has received research support from Indian Council for Medical Research. Dr. SINGH has nothing to disclose. Dr. CHHATTERPAL has nothing to disclose. Dr. Wig has nothing to disclose. Dr. Mittal has nothing to disclose. Mehar Chand Sharma has nothing to disclose. Dr. DAS has nothing to disclose. Ajay Garg has nothing to disclose. Dr. Jagdevan has nothing to disclose. Dr. Shamim has nothing to disclose. Dr. Tripathi has nothing to disclose. Dr. Vibha has nothing to disclose. Rajesh Kumar Singh has nothing to disclose.

Intracranial aspergilloma mimicking metachronous meningioma following transsphenoidal removal of a tuberculum sellae meningioma: illustrative case.

Endoscopic transsphenoidal surgery (eTSS) is a well-established approach for resection of skull-based pathologies such as tuberculum sellae meningiomas; however, central nervous system (CNS) fungal infection is a potential complication, particularly in a patient with concomitant sinusitis. A 58-year-old woman with a tuberculum sellae meningioma causing progressive visual disturbance and concurrent asymptomatic chronic maxillary sinusitis underwent eTSS. Six months later, a de novo dura-based mass with peripheral edema, which was assumed to be an aggressive metachronous meningioma, developed in the middle cranial fossa. The patient underwent frontotemporal craniotomy for complete resection of the lesion, and subsequent histological examination revealed an aspergilloma. She was then treated with an antifungal agent and endoscopic sinus surgery to clear the sinusitis, and no recurrent fungal infection occurred thereafter. CNS fungal infections may appear as a dura-based mass mimicking meningioma. The current case reiterates the importance of the appropriate management of sinusitis prior to eTSS.

Host immune responses in the central nervous system during fungal infections.

Fungal infections in the central nervous system (CNS) cause high morbidity and mortality. The frequency of CNS mycosis has increased over the last two decades as more individuals go through immunocompromised conditions for various reasons. Nevertheless, options for clinical interventions for CNS mycoses are still limited. Thus, there is an urgent need to understand the host-pathogen interaction mechanisms in CNS mycoses for developing novel treatments. Although the CNS has been regarded as an immune-privileged site, recent studies demonstrate the critical involvement of immune responses elicited by CNS-resident and CNS-infiltrated cells during fungal infections. In this review, we discuss mechanisms of fungal invasion in the CNS, fungal pathogen detection by CNS-resident cells (microglia, astrocytes, oligodendrocytes, neurons), roles of CNS-infiltrated leukocytes, and host immune responses. We consider that understanding host immune responses in the CNS is crucial for endeavors to develop treatments for CNS mycosis.

Fungal CNS Infections in Africa: The Neuroimmunology of Cryptococcal Meningitis.

Cryptococcal meningitis (CM) is the leading cause of central nervous system (CNS) fungal infections in humans, with the majority of cases reported from the African continent. This is partly due to the high burden of HIV infection in the region and reduced access to standard-of-care including optimal sterilising antifungal drug treatments. As such, CM is responsible for 10-15% of all HIV-related mortality, with a large proportion being preventable. Immunity to the causative agent of CM, Cryptococcus neoformans, is only partially understood. IFNγ producing CD4+ T-cells are required for the activation of myeloid cells, especially macrophages, to enable fungal killing and clearance. However, macrophages may also act as a reservoir of the fungal yeast cells, shielding them from host immune detection thus promoting latent infection or persistent chronic inflammation. In this chapter, we review the epidemiology and pathogenesis of CNS fungal infections in Africa, with a major focus on CM, and the antifungal immune pathways operating to protect against C. neoformans infection. We also highlight the areas of research and policy that require prioritisation to help reduce the burden of CNS fungal diseases in Africa.

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.

Central Nervous System Fungal Infections in Paediatric Patients

Central Nervous System Fungal Infections in Paediatric Patients

717. Susceptibility to Cryptococcosis in Bruton's Tyrosine Kinase Knockout Model

Abstract Background Patients receiving the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib have an increased likelihood of systemic and central nervous system (CNS) fungal infections. Previous work has shown that BTK knockout (KO) mice have more severe Aspergillus infection compared to wild-type (WT) mice. We sought to determine: 1) if blocking BTK impacted Cryptococcus infection; 2) if the effect was strain-dependent; and 3) if the blood-brain barrier was impaired in BTK KO mice. Methods BTK KO C57 breeding pairs were obtained from Dr. Lionakis (NIH) and expanded in the Duke Breeding Core. We collected 4 clinical C. neoformans isolates from patients who developed cryptococcosis on ibrutinib and used virulent and avirulent control strains (H99 and A1-35-8, respectively). The following doses were used for infection: 1) 5x104 yeast for intranasal (IN); 2) 5x104 for oropharyngeal aspiration (OPA); and 3) 0.1 mL of 5x105 CFU/mL for tail vein injection. Mice were sacrificed on day 7 (IN infection, 6 infection strains; N=35 WT, 80 KO) and day 14 post-infection (OPA infection H99 only; N=15 WT, 20 KO). Lung and brain tissues were collected for yeast census. For tail vein injection, mice were sacrificed 48 hours post-infection (H99 only; N=10 WT, 8 KO). Yeast census was measured by colony forming units (CFUs) per gram of tissue weight. Survival experiments through day 28 were performed for OPA infection with H99 (N=12 WT, 17 KO) and analyzed by Kaplan Meier Curve. Results We observed no difference in infection severity as measured by lung and brain yeast census at days 7 and 14 post-infection or difference in survival between BTK KO and WT mice (Figure 1). We also did not observe a distinct pattern based on Cryptococcus strain to suggest that infection severity was strain-dependent (Figure 1A-B). For tail vein infection, there was no difference in brain yeast census at 48 hours post-infection (Figure 1F). Figure 1. Yeast Census and Survival. A) Lung yeast census day 7 post-intranasal infection with 6 clinical strains and 2 control strains; B) Brain yeast census day 7 post-intranasal infection with 6 clinical strains and 2 control strains; C) Lung yeast census day 14 post infection by oropharyngeal aspiration with H99; D) Brain yeast census day 14 post infection by oropharyngeal aspiration with H99; E) 28 day survival post-infection by oropharyngeal aspiration with H99; F) Brain yeast census 48 hours post infection by tail vein injection. Conclusion Our results in mice suggest that Ibrutinib target BTK is not a major contributing factor for controlling Cryptococcus, and that human susceptibility to cryptococcosis and CNS infection may be due to an off-target effect of ibrutinib. Future work will focus on pharmacologic inhibition of BTK with ibrutinib to determine if the off-target effects of the drug increase risk for cryptococcosis. Disclosures Julia A. Messina, MD, MHS, MS, Uptodate (Other Financial or Material Support) Julia A. Messina, MD, MHS, MS, Uptodate (Individual(s) Involved: Self): Author, Other Financial or Material Support John R. Perfect, MD, Astellas Pharma, Inc. (Consultant, Grant/Research Support, Other Financial or Material Support, Honorarium)Basilea (Consultant, Grant/Research Support)Enzon (Consultant, Grant/Research Support)F2G (Consultant, Grant/Research Support)Merck (Consultant, Research Grant or Support)MethylGene (Consultant, Grant/Research Support)Pfizer, Inc. (Consultant, Grant/Research Support)Schering-Plough Corp. (Consultant, Grant/Research Support)

Fungal Central Nervous System Infections in Patients With COVID-19

Recent studies have indicated that fungal co-infections have a major impact on the morbidity and mortality of patients with COVID-19. In these patients, the excessive production of inflammatory cytokines and the reduction in CD4 + T and CD8 + T cell count entails susceptibility to fungal infections.1 In addition to impaired cell-mediated immunity, comorbidities and immunosuppressive medications have a significant role in the development of fungal infections and have serious impacts on clinical outcomes.1-3

Neuroimaging findings of posterior reversible encephalopathy syndrome (PRES) following haematopoietic stem cell transplantation in paediatric recipients

BackgroundHaematopoietic stem cell transplantation (HSCT) is used worldwide in various malignant and nonmalignant childhood diseases, including haematologic, genetic, autoimmune and metabolic disorders, and is the only curative treatment for many of these illnesses. The survival rates of many childhood diseases have been increased due to HSCT treatment. However, associated complications are still important for management. Central nervous system (CNS) complications in paediatric HSCT recipients can be associated with high morbidity and significantly contribute to mortality. Posterior reversible encephalopathy syndrome (PRES) is one of the most common CNS complications in patients with neurological symptoms following HSCT. Magnetic resonance imaging (MRI) is the modality of choice and shows typical bilateral vasogenic oedema at the posterior parts of the cerebral hemispheres; however, various atypical imaging manifestations can also occur. In this study, we retrospectively examined CNS complications in our paediatric HSCT recipients with a focus on the typical and atypical neuroimaging manifestations of PRES following HSCT.MethodsWe retrospectively reviewed the medical records of 300 consecutive paediatric HSCT recipients from January 2014 to November 2018. A total of 130 paediatric HSCT recipients who experienced neurological signs and symptoms and were evaluated with neuroimaging studies following HSCT were enrolled in the study. The timing of CNS complications was defined according to immune status, including the pre-engraftment period (< 30 days after HSCT), the early postengraftment period (30–100 days after HSCT), and the late postengraftment period (> 100 days after HSCT), which were defined as phases 1, 2 and 3, respectively.ResultsOverall, 130 paediatric HSCT recipients experienced neurological signs and symptoms and therefore underwent neuroimaging examinations. Among these 130 patients, CNS complications were present in 23 patients (17.6%, 23/130), including 13 (56.5%) females and 10 (43.5%) males with a median age of 8.0 years (range, 8 months to 18.0 years). Among these 23 patients, 14 cases of PRES (60.9%), 5 (21.7%) cases of leukoencephalopathy, 3 cases of acute subdural haemorrhage (ASDH) (13%) and 1 (4.3%) case of fungal CNS infection were identified by neuroimaging. On MRI, typical parietooccipital vasogenic oedema was present in 78.5% of the PRES cases (11/14). The following atypical neuroimaging manifestations were observed: isolated involvement of the bilateral frontal lobes in 1 case, isolated cerebellar vermis involvement in 1 case, and isolated basal ganglia involvement in 1 case. Restricted diffusion associated with cytotoxic damage was demonstrated in 2 of 14 cases, one of which also showed subacute cytotoxic injury with ADC pseudonormalization.ConclusionPaediatric HSCT recipients presenting with CNS signs and symptoms should be evaluated by neuroimaging studies for timely diagnosis and early management. PRES is the most common CNS complication and may present with atypical MRI manifestations, which should not dissuade a PRES diagnosis in appropriate clinical settings.

Safic-Alcan extends distribution agreement with PMC Organometallix

A fungal central nervous system (CNS) infection develops after it spreads from somewhere else in the body to the brain or spinal cord. Fungal CNS infection is associated with immune system impairment, some health conditions including the use of the medications (e.g., steroids), surgical procedures, Human immunodeficiency virus (HIV) infection, organ transplantation, end stage renal disease on hemodialysis, status post chemotherapy, neutropenia, and pre-term babies. Fungi involved in brain infection include yeasts such as Cryptococcus sp., Candida sp., and Trichosporon spp.; Moniliaceous molds including Aspergillus sp., Fusarium sp. and Scedosporium sp., Mucoromycetes such as Mucor spp. and Rhizopus spp., dimorphic fungi including Blastomyces sp., Coccidioides spp. and Histoplasma sp., and dematiaceous fungi such as Cladophialophora sp. and Exophiala sp. In this article, we will focus on the fungal meningitis and encephalitis. We will also explain fungal invasion mechanisms, the CNS immune response to the fungal infection, and clinical consequences.

MR vessel wall imaging in cerebral bacterial and fungal infections.

PurposeCentral nervous system (CNS) bacterial and fungal infections can cause secondary vasculitis which worsens the prognosis due to development of complications like infarctions or hemorrhages. In this prospective study, we aim to study intracranial vessel wall imaging findings in bacterial and fungal infections.MethodsWe included 12 cases of nontubercular bacterial and fungal CNS infections each, in whom definitive microbiological diagnosis could be made. High-resolution vessel wall imaging (VWI) and time of flight MR angiography (TOF MRA) were incorporated in the routine imaging protocol. All cases were evaluated for the presence of vascular enhancement, pattern of enhancement, and stenosis on VWI. Statistical analysis was done to evaluate association between findings of vessel wall imaging and infarctions.ResultsWe found infarctions in 5 out of 12 cases (41.7%) of the bacterial group and 7 out of 12 cases (58.3%) of the fungal group. Vessel wall enhancement was seen in 5 cases (41.7%) of the bacterial group and 9 cases (75%) of the fungal group. There was a significant association between infarctions and vessel wall enhancement in the fungal group. However, pattern of enhancement or stenosis on VWI was not significantly associated with presence of infarction. VWI detected more cases of vascular involvement than TOF MRA.ConclusionSecondary infectious vasculitis in bacterial and fungal infections can be detected by VWI, which can play an important role in better patient management as detection of vascular involvement can prompt early treatment to prevent complications like infarctions or hemorrhages.

Next generation sequencing for diagnosis of central nervous system aspergillosis in liver transplant recipients.

BackgroundFungal encephalitis is uncommon and sometimes fatal in liver transplant (LT) recipients. Early diagnosis of central nervous system (CNS) fungal infections, especially aspergillosis, is difficult based on routine tests of cerebrospinal fluid (CSF) alone. Next-generation sequencing (NGS) as a new tool may help in this respect.MethodsShotgun metagenomics was used to detect pathogens in CSF of patients, who were clinically suspected of CNS infection. Sequencing was performed at BGIseq-50 platform (BGI, Shenzhen).ResultsNGS technique identified Aspergillus in CSF of 5 patients, who were suspected of CNS infection, although clinical symptoms of these patients varied dramatically. The resulting sequence reads corresponding to Aspergillus species ranged from 2 to 25, with genomic coverage ranging from 0.0003% to 0.0036%. Rapid identification of Aspergillus enabled early appropriate antifungal therapy, although 4 patients eventually died of severe infection.ConclusionsThis is the first study to highlight the utility of NGS in early diagnosis of CNS aspergillosis in LT recipients. This new tool may be helpful in improving the diagnosis of CNS aspergillosis.

Imaging of CNS Fungal Infections: Review Article

Fungal infections of the central nervous system (CNS) are usually identified in immunocompromised patients but rare in immunocompetent hosts. The clinical and imaging manifestations are mainly influenced by types of fungal pathogen and immune status of the patients. The CNS fungal infections can develop through hematogenous dissemination from primary site of infection, cerebrospinal fluid seeding, or direct extension from adjacent sources of infection. Fungal infections can result in meningitis, meningoencephalitis, cerebritis, granuloma, or abscess formation, which imaging findings are often non-specific and difficult to distinguish from bacterial or tuberculous infection, non-infectious inflammatory disease, or even intracranial neoplasm. Vascular complications including vasculitis, cerebral infarction, or mycotic aneurysm are commonly present due to angioinvasion of fungal hyphae. In addition, some characteristic imaging features of fungal infections can be identified by computed tomography (CT) or magnetic resonance imaging (MRI), such as intracavitary projections in fungal abscesses and gelatinous pseudocysts in cryptococcosis that could help suggest the diagnosis. Recognizing the imaging findings of common intracranial fungal infections combined with appropriate clinical setting is crucial for allowing early diagnosis and leading to early specific treatment. The present article reviewed common imaging findings of CNS fungal infections and distinct imaging features of specific pathogens. Keywords: Fungal infection, Brain abscess, Cryptococcosis, Central nervous system (CNS), Computed tomography (CT), Diffusion weighted imaging (DWI), Magnetic resonance imaging (MRI)

Antifungal drugs: An updated review of central nervous system pharmacokinetics.

Invasive fungal infections (IFIs) in the central nervous system (CNS) are particularly hard to treat and are associated with high morbidity and mortality rates. Four chemical classes of systemic antifungal agents are used for the treatment of IFIs (eg meningitis), including polyenes, triazoles, pyrimidine analogues and echinocandins. This review will address all of these classes and discuss their penetration and accumulation in the CNS. Treatment of fungal meningitis is based on the antifungal that shows good penetration and accumulation in the CNS. Pharmacokinetic data concerning the entry of antifungal agents into the intracranial compartments are faulty. This review will provide an overview of the ability of systemic antifungals to penetrate the CNS, based on previously published drug physicochemical properties and pharmacokinetic data, for evaluation of the most promising antifungal drugs for the treatment of fungal CNS infections. The studies selected and discussed in this review are from 1990 to 2019.

Role of Voriconazole in the Management of Invasive Central Nervous System Aspergillosis: A Case Series from a Tertiary Care Centre in India

Invasive central nervous system (CNS) aspergillosis is acquired by either hematogenous dissemination or direct spread from a sinus infection. We describe a series of nine patients with CNS aspergillosis from a tertiary care teaching institute in North India who were treated with voriconazole alone or in combination with surgery. All patients who had clinical and radiological features consistent with fungal CNS infection, showed the presence of septate hyphae on histopathology/microscopy and were either culture positive for Aspergillus spp. or had serum galactomannan positivity were diagnosed as CNS aspergillosis. Clinical features, risk factors, diagnostic modalities, treatment details and outcome at last follow-up were recorded for all patients diagnosed with CNS aspergillosis. A total of nine patients were diagnosed with CNS aspergillosis. The median duration of presentation at our hospital was six months (IQR-2-9 months). Six patients had concomitant sinus involvement, while two patients had skull-base involvement as well. All patients were treated with voriconazole therapy, and three of these patients underwent surgery. All but one patient survived at the last follow-up (median duration was 14 months (IQR- 8-21.5). Two patients had complete resolution, and voriconazole was stopped at the last follow-up, and the rest of the patients were continued on voriconazole. Of the six patients who were continued on voriconazole, all but one had more than 50% radiological resolution on follow-up imaging. Invasive CNS aspergillosis is an important cause of CNS fungal infection that is often diagnosed late and requires long-term voriconazole-based therapy.

Cerebral phaeohyphomycosis due to Cladophialophora bantiana in an immunocompetent individual: A case report and brief review of literature

Background and Purpose: Fungal infections of the central nervous system (CNS) are life-threatening conditions that are frequently misdiagnosed with bacterial and viral CNS infections. Cerebral phaeohyphomycosis is a cerebral infection caused by dematiaceous fungi, especially Cladophialophora bantiana. Very few cases of fungal CNS infection have been reported across the world. High clinical suspicion should be cast for the patients with brain abscess that do not respond to conventional antibiotic therapy.Case report: We report a case of a 21-year-old male presenting with headache, seizures and weakness in the limbs. Radiological examination revealed multiple brain abscesses. After surgical excision and laboratory evaluation, it was found to be caused by C. bantiana. The patient’s outcome was good with surgical excision and voriconazole therapy.Conclusion: Brain abscess caused by C. bantiana is on rise, especially in immunocompromised groups. Thus, high clinical suspicion, accurate diagnosis and management are the fundamentals for good prognosis.