Cats with central nervous system cryptococcosis

Background: Cryptococcosis is a serious fungal infection contracted by humans and animals, and the most common systemic mycosis found in cats. This disease is often contracted through inhalation of fungal propagules. The Central Nervous System (CNS) may be infected through local extension (nasal and frontal sinuses) or via hematogenous route. Similarly to CNS bacterial infection, the clinical signs of neurological dysfunction may be attributed to mass effect (gelatinous mass of fungal microorganisms and fungal granuloma formation) or to a more disseminated inflammatory response to invading microorganisms. The objective of this study is to report one case of a patient with cryptococcal granulomas in the central nervous system and one case of a patient with neurological signs associated to a cryptococcosis. Cases: Case 1. A 3-year-old male mixed breed feline was admitted to a veterinary clinic, located in Porto Alegre, RS, Southern Brazil. The patient presented unsourced behavioral changes, vestibular ataxia and dysphagia caused by inability of coordination. The following tests were performed: complete blood count test, biochemical analysis, computed tomography scan (CT scan), fluid analysis, radiography and toxoplasmosis test. The following medicine were administrated for treatment: fluconazole, dexamethasone, mannitol, phenobarbital and levetiracetam. Fluid therapy was also part of the treatment. Immediately after death, the cat was submitted for necropsy, and a fungal granulomatous meningoencephalomyelitis was diagnosed. Cryptococcus sp. was identified as the causal agent through pathological findings, fungal culture and PCR analysis. Case 2. One year later, another feline was admitted to the same clinic (a 2-year-old female mixed breed) presenting hypersalivation, tremors and excessive vocalization. The patient had contact with the deceased feline. The following tests were performed: complete blood count...(AU)

Severe COVID-19 Cases: Is Respiratory Distress Partially Explained by Central Nervous System Involvement?

The main characteristics and challenging symptoms of COVID-19, caused by the novel coronavirus SARS-CoV-2, are related to re-spiratory distress. Although most patients have mild symptoms such as fever, headache, cough, myalgia and anosmia, some develop acute respiratory distress syndrome, leading to death in many cases. Human coronavirus (CoVs) were responsible for two previ-ous worldwide outbreaks: Severe Acute Respiratory Syndrome (SARS-CoV) and Middle East Respiratory Syndrome (MERS-CoV). Several reports of these outbreaks demonstrated that these diseases affected the central nervous system (CNS).[1] Thus, for the current COVID-19 pandemic, a crucial question arises: does CNS affection at least partially explain the respiratory distress commonly found in these patients?

Cats with central nervous system cryptococcosis

Background: Cryptococcosis is a serious fungal infection contracted by humans and animals, and the most common systemic mycosis found in cats. This disease is often contracted through inhalation of fungal propagules. The Central Nervous System (CNS) may be infected through local extension (nasal and frontal sinuses) or via hematogenous route. Similarly to CNS bacterial infection, the clinical signs of neurological dysfunction may be attributed to mass effect (gelatinous mass of fungal microorganisms and fungal granuloma formation) or to a more disseminated inflammatory response to invading microorganisms. The objective of this study is to report one case of a patient with cryptococcal granulomas in the central nervous system and one case of a patient with neurological signs associated to a cryptococcosis. Cases: Case 1. A 3-year-old male mixed breed feline was admitted to a veterinary clinic, located in Porto Alegre, RS, Southern Brazil. The patient presented unsourced behavioral changes, vestibular ataxia and dysphagia caused by inability of coordination. The following tests were performed: complete blood count test, biochemical analysis, computed tomography scan (CT scan), fluid analysis, radiography and toxoplasmosis test. The following medicine were administrated for treatment: fluconazole, dexamethasone, mannitol, phenobarbital and levetiracetam. Fluid therapy was also part of the treatment. Immediately after death, the cat was submitted for necropsy, and a fungal granulomatous meningoencephalomyelitis was diagnosed. Cryptococcus sp. was identified as the causal agent through pathological findings, fungal culture and PCR analysis. Case 2. One year later, another feline was admitted to the same clinic (a 2-year-old female mixed breed) presenting hypersalivation, tremors and excessive vocalization. The patient had contact with the deceased feline. The following tests were performed: complete blood count...

Cryptococcal dissemination to the central nervous system requires the vacuolar calcium transporter Pmc1.

Cryptococcus neoformans is a basidiomycetous yeast and the cause of cryptococcosis in immunocompromised individuals. The most severe form of the disease is meningoencephalitis, which is one of the leading causes of death in HIV/AIDS patients. In order to access the central nervous system, C. neoformans relies on the activity of certain virulence factors such as urease, which allows transmigration through the blood-brain barrier. In this study, we demonstrate that the calcium transporter Pmc1 enables C. neoformans to penetrate the central nervous system, because the pmc1 null mutant failed to infect and to survive within the brain parenchyma in a murine systemic infection model. To investigate potential alterations in transmigration pathways in these mutants, global expression profiling of the pmc1 mutant strain was undertaken, and genes associated with urease, the Ca2+ -calcineurin pathway, and capsule assembly were identified as being differentially expressed. Also, a decrease in urease activity was observed in the calcium transporter null mutants. Finally, we demonstrate that the transcription factor Crz1 regulates urease activity and that the Ca2+ -calcineurin signalling pathway positively controls the transcription of calcium transporter genes and factors related to transmigration.

Neurological and multiple organ involvement due to Paracoccidioides brasiliensis and HIV co-infection diagnosed at autopsy.

Paracoccidioidomycosis (PCM), caused by Paracoccidioides brasiliensis, is the most prevalent systemic mycosis among immunocompetent patients in Latin America; it is rare in immunocompromised patients. The estimated frequency of central nervous system (CNS) involvement in the HIV/PCM population was 2.5%. We report a case of HIV/P. brasiliensis co-infection, with neurological (NPCM) and multiple organ involvement, indicating a diagnosis of AIDS. PCM diagnosis was established during the autopsy. This is the first described case of HIV/P. brasiliensis co-infection with CNS involvement diagnosed at autopsy. In conclusion, the diagnosis of NPCM is challenging, and it must be considered in the differential diagnosis in HIV-positive patients who reside in or have visited areas in which the condition is endemic and who present with neurological symptoms.

Streptococcus agalactiae impairs cerebral bioenergetics in experimentally infected silver catfish.

It is becoming evident that bacterial infectious diseases affect brain energy metabolism, where alterations of enzymatic complexes of the mitochondrial respiratory chain and creatine kinase (CK) lead to an impairment of cerebral bioenergetics which contribute to disease pathogenesis in the central nervous system (CNS). Based on this evidence, the aim of this study was to evaluate whether alterations in the activity of complex IV of the respiratory chain and CK contribute to impairment of cerebral bioenergetics during Streptococcus agalactiae infection in silver catfish (Rhamdia quelen). The activity of complex IV of the respiratory chain in brain increased, while the CK activity decreased in infected animals compared to uninfected animals. Brain histopathology revealed inflammatory demyelination, gliosis of the brain and intercellular edema in infected animals. Based on this evidence, S. agalactiae infection causes an impairment in cerebral bioenergetics through the augmentation of complex IV activity, which may be considered an adaptive response to maintain proper functioning of the electron respiratory chain, as well as to ensure ongoing electron flow through the electron transport chain. Moreover, inhibition of cerebral CK activity contributes to lower availability of ATP, contributing to impairment of cerebral energy homeostasis. In summary, these alterations contribute to disease pathogenesis linked to the CNS.

Experimental autoimmune encephalomyelitis development is aggravated by Candida albicans infection.

Multiple sclerosis (MS) is an inflammatory/autoimmune disease of the central nervous system (CNS) mainly mediated by myelin specific T cells. It is widely believed that environmental factors, including fungal infections, contribute to disease induction or evolution. Even though Candida infection among MS patients has been described, the participation of this fungus in this pathology is not clear. The purpose of this work was to evaluate the effect of a Candida albicans infection on experimental autoimmune encephalomyelitis (EAE) that is a widely accepted model to study MS. Female C57BL/6 mice were infected with C. albicans and 3 days later, animals were submitted to EAE induction by immunization with myelin oligodendrocyte glycoprotein. Previous infection increased the clinical score and also the body weight loss. EAE aggravation was associated with expansion of peripheral CD4(+) T cells and production of high levels of TNF-α, IFN-γ IL-6, and IL-17 by spleen and CNS cells. In addition to yeast and hyphae, fungus specific T cells were found in the CNS. These findings suggest that C. albicans infection before EAE induction aggravates EAE, and possibly MS, mainly by CNS dissemination and local induction of encephalitogenic cytokines. Peripheral production of encephalitogenic cytokines could also contribute to disease aggravation.

Communication between gastrointestinal bacteria and the nervous system.

In the past few years, intestinal microbiota has emerged as a novel target for the treatment of gut-brain axis alterations. These include functional gastrointestinal disorders, such as irritable bowel syndrome (IBS), which can be comorbid with stress-related psychiatric conditions. Thus, modulation of the microbiota (e.g. with the use of probiotics) could be proposed as a novel strategy not only for the treatment of IBS but also as an adjuvant for psychiatric treatment of anxiety and depression.

Gut-central nervous system axis is a target for nutritional therapies.

Historically, in the 1950s, the chemist Linus Pauling established a relationship between decreased longevity and obesity. At this time, with the advent of studies involving the mechanisms that modulate appetite control, some researchers observed that the hypothalamus is the "appetite centre" and that peripheral tissues have important roles in the modulation of gut inflammatory processes and levels of hormones that control food intake. Likewise, the advances of physiological and molecular mechanisms for patients with obesity, type 2 diabetes mellitus, inflammatory bowel diseases, bariatric surgery and anorexia-associated diseases has been greatly appreciated by nutritionists. Therefore, this review highlights the relationship between the gut-central nervous system axis and targets for nutritional therapies.

Estudio del polimorfismo genético de las células de la médula ósea y del sistema nervioso central de ratas mediante la técnica de RAPD / Study of genetic polymorphism of the bone marrow and the central nervous system of rats cells by RAPD technique

Los modelos experimentales en rata han sido de gran utilidad en las evaluaciones terapéuticas o de reemplazo de células en enfermedades neurodegenerativas. Se ha comprobado que las células de la médula ósea (CMO) de ratas pueden diferenciarse en células que no forman parte de sus linajes normales. Hay evidencias de estos procesos de trans-diferenciación, pero aún no se conocen los mecanismos moleculares que activan estos procesos. El propósito de nuestro trabajo fue estudiar el polimorfismo genético del ADN de los tipos celulares que conforman las CMO y las células del sistema nervioso central (SNC), estríatales y de la corteza de ratas mediante la técnica de RAPD. Las CMO, las células mononucleares (CMMO), las células estromales (CEMO) y las del SNC fueron obtenidas de ratas, y su ADN genómico fue purificado y amplificado mediante la técnica de RAPD, utilizando 15 cebadores al azar. Se construyó un dendograma de las bandas de amplificación generadas utilizando el método de UPGMA. Las células estudiadas según el análisis del RAPD quedaron en 2 grupos bien definidos, pudiéndose diferenciar las CEMO del resto de las células estudiadas. Los cebadores OPA-6, 7 y 12, mostraron el polimorfismo genético de los linajes de células estudiadas. Mediante la técnica de RAPD se demostró la variabilidad genética entre las CEMO y las CMMO, células estriadas y de corteza que mostraron una homogeneidad genética, proponiéndose marcadores específicos de RAPD para cada grupo de células. Este es el primer estudio del polimorfismo genético de las CMO y del SNC de ratas.

Experimental models have been of grate usefulness in the therapeutic or replacement cells in neurodegenerative diseases. It has been demonstrated that bone marrow cells (BMC), can be difefferentiated in cells that do not form part of their normal lineage. There is evidence of these trans-differentiation processes in these cells, but nevertheless, molecular mechanisms that activate these differentiation process still not known. The purpose of our work was to study the genetic polymorphism of those cellular types; that conform the rat bone marrow cells (BMC) as well as those of the central nervous system (CNS), striatum cells and cortex ones, trough RAPD technique. BM, mononuclear cells (BMMC), estromal cells (BMSC) and the CNS cells were obtained from rats and genomic ADN was purified and amplified through RAPD technique, using 15 random primers. A dendogram was constructed according to UPGMA method of the amplifying RAPD bands. Studied cells as- according to the RAPD analysis- were grouped into 2 well- defined groups, as CEMO coud be differentiated from the rest of studied cells. OPA-6, 7 and 12 primers showed the genetic polymorphism of the studied lineages cells. Also will be proposed specific RAPD genetic markers. Through RAPD technique permitted the genetic variability was demonstrated betwen BMEC and BMMC of striated cells and of cortex, which demonstratd a genetic homogeneity through RAPD technique so specific genetic markers of RAPD were thus propose for each group of cells. These constitute the first study on genetic polymorphism of BMC and CNS.

Compromiso neurológico por Mycoplasma pneumoniae en niños: Experiencia del Hospital Nacional Cayetano Heredia / Neurological disorders by Mycoplasma pneumoniae in Children: The experience of Hospital Nacional Cayetano Heredia

Introducción: Las complicaciones neurológicas por Mycoplasma pneumoniae han sido descritas desde hace más de 50 años. Este microorganismo puede causar entre 5 y 10 por ciento del total de infecciones del sistema nervioso central. En Perú, esta enfermedad es subdiagnosticada debido a la falta de sospecha clínica.Objetivos: Describir las características clínicas y de laboratorio de los pacientes con afección del sistema nervioso central por M. pneumoniae, diagnosticados en el Hospital Nacional Cayetano Heredia. Material y métodos: Se revisó la base de datos de la Unidad de Neurología Pediátrica y el libro de egresos del Departamento de Pediatría del Hospital Nacional Cayetano Heredia. Se incluyó a todos los pacientes con compromiso neurológico por M. pneumoniae. Se recopilaron datos clínicos y epidemiológicos. Resultados: Se identificaron 8 pacientes. Tres presentaron mielitis, cuatro presentaron encefalitis y una niña tuvo encefalitis y mielitis. El diagnóstico se estableció por serología IgM. Los pacientes con encefalitis tuvieron frecuentes secuelas neurológicas. En el grupo de mielitis, excepto una niña con localización cervical, todos evolucionaron favorablemente. Los niños con encefalitis fueron más sintomáticos, llegando al estado de coma con necesidad de soporte ventilatorio y crisis epilépticas de difícil control. Conclusiones: Las infecciones del sistema nervioso central por M. pneumoniae existen en nuestro medio y son poco diagnosticadas. Deben formar parte del enfoque diagnóstico de cualquier paciente con afección aguda y subaguda del sistema nervioso central para detectarla precozmente y evaluar opciones terapéuticas.

Introduction: Neurological complications of Mycoplasma pneumoniae have been described for more than 50 years. This microorganism can cause between 5 and 10 per cent of the infections of Central Nervous System. In Peru, this disease is subdiagnosed due to lack of clinical suspicion. Objectives: To describe the clinic and laboratorial characteristics of patients with M. pneumoniae CNS commitment, diagnosed in the Cayetano Heredia National Hospital. Material and methods: The Database of the Unit of Neuropediatrics and the Register of Discharges from the HNCH were reviewed. We include all the patients with neurological commitment by M. pneumoniae. The clinical and epidemiologic data were compiled.Results: There were 8 patients identified. Three children underwent myelitis, four had encephalitis and one girl presented encephalitis and myelitis. The diagnosis was stablished by positive IgM serology. The patients with encephalitis had high percentage of neurological sequelaes. In the myelitis group, except a girl with cervical location, all evolved favorably. Children with encephalitis were much more symptomatic, arriving at the state of coma with ventilatory support requirement and difficult-to-control seizures. Conclusions: Central nervous system infections due to M. pneumoniae do exist in our own environment but are infrequently diagnosed. They should be suspected upon in any patient with acute or subacute infection of the central nervous system to afford early diagnosis and treatment.

Virulence profile of strains of Cryptococcus neoformans var. grubii evaluated by experimental infection in BALB/c mice and correlation with exoenzyme activity.

To evaluate the virulence profile of strains of Cryptococcus neoformans var. grubii, 62 strains of this yeast were inoculated into BALB/c mice. It was found that 69 % of the strains were significantly more lethal to the mice and were recovered from a higher percentage (60 %) of the organs compared with the other 31 % of the strains, which were recovered from 35 % of organs tested. Those strains that provoked higher death rates were also recovered from the central nervous system at a higher rate (84 %) than the less lethal strains (32 %). This finding led to an investigation of the factors that enhanced the capacity for neurological infection and death of the animals. The results of this study suggested that environmental strains present different degrees of virulence. The correlation of exoenzyme production before and after inoculation and between the groups of mice indicated that exoenzyme production had no influence on differences in virulence among the strains studied.

[Role of the Shiga toxin in the hemolytic uremic syndrome]. / Papel de la toxina shiga en el síndrome urémico hemolítico.

In the last years, infection associated with Shiga toxin-producing Escherichia coli (STEC) and subsequent Hemolitic-Uremic Syndrome (HUS) became relevant as a public health since it was considered as one of the most important emergent patogen present in the food contaminated by cattle feces. STEC infection may be asymptomatic or begins with a watery diarrhea that may or may not progress to bloody diarrhea (hemorrhagic colitis) and HUS. In Argentina, HUS is the most common pediatric cause of acute renal insufficiency and the second cause of chronic renal failure. Up to now, STEC infection lacks of known effective treatment strategies that diminish risk of progression to HUS. The mechanisms by which Shiga toxin (Stx) induce HUS may help to find strategies to prevent or ameliorate HUS. In this article, recent progress that has contributed to understanding the disease pathogenesis of STEC is reviewed. New strategies to prevent further uptake of Shiga from the gut, either during the diarrheal phase or once HUS has developed are discussed.

Papel de la Toxina Shiga en el sindrome urémico hemolítico / Role of the Shiga toxin in the hemolytic uremic syndrome

In the last years, infection associated with Shiga toxin-producing Escherichia coli (STEC) and subsequent Hemolitic-Uremic Syndrome (HUS) became relevant as a public health since it was considered as one of the most important emergent patogen present in the food contaminated by cattle feces. STEC infection may be asymptomatic or begins with a watery diarrhea that may or may not progress to bloody diarrhea (hemorrhagic colitis) and HUS. In Argentina, HUS is the most common pediatric cause of acute renal insufficiency and the second cause of chronic renal failure. Up to now, STEC infection lacks of known effective treatment strategies that diminish risk of progression to HUS. The mechanisms by which Shiga toxin (Stx) induce HUS may help to find strategies to prevent or ameliorate HUS. In this article, recent progress that has contributed to understanding the disease pathogenesis of STEC is reviewed. New strategies to prevent further uptake of Shiga from the gut, either during the diarrheal phase or once HUS has developed are discussed.

Papel de la Toxina Shiga en el sindrome urémico hemolítico / Role of the Shiga toxin in the hemolytic uremic syndrome

In the last years, infection associated with Shiga toxin-producing Escherichia coli (STEC) and subsequent Hemolitic-Uremic Syndrome (HUS) became relevant as a public health since it was considered as one of the most important emergent patogen present in the food contaminated by cattle feces. STEC infection may be asymptomatic or begins with a watery diarrhea that may or may not progress to bloody diarrhea (hemorrhagic colitis) and HUS. In Argentina, HUS is the most common pediatric cause of acute renal insufficiency and the second cause of chronic renal failure. Up to now, STEC infection lacks of known effective treatment strategies that diminish risk of progression to HUS. The mechanisms by which Shiga toxin (Stx) induce HUS may help to find strategies to prevent or ameliorate HUS. In this article, recent progress that has contributed to understanding the disease pathogenesis of STEC is reviewed. New strategies to prevent further uptake of Shiga from the gut, either during the diarrheal phase or once HUS has developed are discussed.(AU)

Candidiasis urinaria y cerebral en un neonato con malformación urinaria bilateral congénita: hallazgos ultrasonográficos / Neonatal brain and urinary candidal infection: US findings

El pronóstico de este trabajo es describir los hallazgos ecográficos y demostrar la utilidad del ultrasonido en el diagnóstico precoz de la candidiasis urinaria y cerebral, por lo que realizamos ecografía prenatal de una paciente en la que se diagnosticó la presencia de un feto con uronefrosis bilateral congénita y ecografías tempranas al neonato pretérmino. La detección por US de la presencia de bolas fúngicas dentro de la vía excretora previamente dilatada fue determinante para realizar el cateterismo de ambos uréteres por medio del cual se obtuvo material para cultivo y sirvió para derivación urinaria. Concluimos que el US es el mejor método de diagnóstico por imágenes para ser utilizado en los neonatos prematuros de bajo peso y de alto riesgo

Candidiasis urinaria y cerebral en un neonato con malformación urinaria bilateral congénita: hallazgos ultrasonográficos / Neonatal brain and urinary candidal infection: US findings

El pronóstico de este trabajo es describir los hallazgos ecográficos y demostrar la utilidad del ultrasonido en el diagnóstico precoz de la candidiasis urinaria y cerebral, por lo que realizamos ecografía prenatal de una paciente en la que se diagnosticó la presencia de un feto con uronefrosis bilateral congénita y ecografías tempranas al neonato pretérmino. La detección por US de la presencia de bolas fúngicas dentro de la vía excretora previamente dilatada fue determinante para realizar el cateterismo de ambos uréteres por medio del cual se obtuvo material para cultivo y sirvió para derivación urinaria. Concluimos que el US es el mejor método de diagnóstico por imágenes para ser utilizado en los neonatos prematuros de bajo peso y de alto riesgo (AU)

The invasive behaviour of Cryptococcus neoformans: a possibility of direct access to the central nervous system?

Cryptococcocal meningoencephalitis is always considered secondary to initial lung infection. Because of the unquestionable evidence of haematogenious spread from the lungs, few publications have reported about other possible primary sites of infection or other routes to the central nervous system. This study was designed to investigate the infiltrative pattern of C. neoformans in immunocompromised mice by treatment with dexamethasone. The infection was performed by nasal instillation (30 mice) or injection into the retro-orbital space (12 mice). From the group infected intranasally, 3 mice presented diffuse invasive fungal colonisation of the mucosa and submucosa. The histologic findings showed infiltrative growth along the periosteum, sometimes surrounded nervous endings of submucosa, invasion along the olfactory nerve and simultaneous meningeal involvement in 2 mice on the 6th and 8th day of infection. All mice infected into the retro-ocular space developed lesions containing numerous cryptococci in the local of the inoculum. Out of the main lesion we observed preferential growth along the perineural spaces with adherence to the perineurium, perivascular spaces and sometimes along aponeurosis. Simultaneous invasion of trigeminal ganglio and trigeminal branches was observed in 4 mice. These morphologic patterns suggest the hypothesis of direct infiltrative invasion of the central nervous system.

Pathogenesis of Venezuelan equine encephalitis virus infection in mice and hamsters.

The pathogenesis of Venezuelan equine encephalitis (VEE) virus infection was compared in intraperitoneally inoculated mice (n = 24, 6 to 8 weeks old) and hamsters (n = 9, 90-110 g) using histopathology and immunohistochemical localization of VEE virus antigen. Infected mice developed paralysis, and the majority died by 9 days after inoculation. In contrast, hamsters did not survive beyond 3 days after inoculation, and they did not develop any neurologic signs. VEE virus antigen, demonstrated by immunoperoxidase staining, and pathologic changes were present in extraneural organs of both mice and hamsters. There was more severe involvement in hamsters, particularly in Peyer's patches of the distal small intestine. There was a severe encephalomyelitis in mice, but pathologic changes were not well established in the brains of hamsters before death. VEE virus antigen was widespread in the central nervous system of both mice and hamsters. VEE virus was found to be highly neurotropic in hamsters and had a similar distribution in the brain as in mice, but hamsters died from their extraneural disease before major central nervous system disease developed.