Search

Background: Breakthrough invasive fungal infections (bIFIs) are an area of concern in the scarcity of new antifungals. The mixed form of bIFIs is a rare phenomenon but could be potentially a troublesome challenge when caused by azole-resistant strains or non-Aspergillus fumigatus. To raise awareness and emphasize diagnostic challenges, we present a case of mixed bIFIs in a child with acute lymphoblastic leukemia., Case Presentation: A newly diagnosed 18-month-old boy with acute lymphoblastic leukemia was complicated with prolonged severe neutropenia after induction chemotherapy. He experienced repeated episodes of fever due to extended-spectrum beta-lactamase-producing Escherichia coli bloodstream infection and pulmonary invasive fungal infection with Aspergillus fumigatus (early-type bIFIs) while receiving antifungal prophylaxis. Shortly after pulmonary involvement, his condition aggravated by abnormal focal movement, loss of consciousness and seizure. Cerebral aspergillosis with Aspergillus niger diagnosed after brain tissue biopsy. The patient finally died despite 108-day antifungal therapy., Conclusions: Mixed bIFIs is a rare condition with high morbidity and mortality in the patients receiving immunosuppressants for hematological malignancies. This case highlights the clinical importance of Aspergillus identification at the species level in invasive fungal infections with multiple site involvement in the patients on antifungal prophylaxis.

We report here the effects of hydrogen sulfide (sulfide), that accumulates in ETHE1 deficiency, in rat cerebellum. Sulfide impaired electron transfer and oxidative phosphorylation. Sulfide also induced mitochondrial swelling, and decreased ΔΨm and calcium retention capacity in cerebellum mitochondria, which were prevented by cyclosporine A (CsA) plus ADP, and ruthenium red, suggesting mitochondrial permeability transition (mPT) induction. Melatonin (MEL) and N-ethylmaleimide also prevented sulfide-induced alterations. Prevention of sulfide-induced decrease of ΔΨm and viability by CsA and MEL was further verified in cerebellum neurons. The data suggest that sulfide induces mPT pore opening via thiol modification and ROS generation., (Copyright © 2018 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)

Early-life infection has been shown to have profound effects on the brain and behavior across the lifespan, a phenomenon termed "early-life programming". Indeed, many neuropsychiatric disorders begin or have their origins early in life and have been linked to early-life immune activation (e.g. autism, ADHD, and schizophrenia). Furthermore, many of these disorders show a robust sex bias, with males having a higher risk of developing early-onset neurodevelopmental disorders. The concept of early-life programming is now well established, however, it is still unclear how such effects are initiated and then maintained across time to produce such a phenomenon. To begin to address this question, we examined changes in microglia, the immune cells of the brain, and peripheral immune cells in the hours immediately following early-life infection in male and female rats. We found that males showed a significant decrease in BDNF expression and females showed a significant increase in IL-6 expression in the cerebellum following E.coli infection on postnatal day 4; however, for most cytokines examined in the brain and in the periphery we were unable to identify any sex differences in the immune response, at least at the time points examined. Instead, neonatal infection with E.coli increased the expression of a number of cytokines in the brain of both males and females similarly including TNF-α, IL-1β, and CD11b (a marker of microglia activation) in the hippocampus and, in the spleen, TNF-α and IL-1β. We also found that protein levels of GRO-KC, MIP-1a, MCP1, IP-10, TNF-α, and IL-10 were elevated 8-hours postinfection, but this response was resolved by 24-hours. Lastly, we found that males have more thin microglia than females on P5, however, neonatal infection had no effect on any of the microglia morphologies we examined. These data show that sex differences in the acute immune response to neonatal infection are likely gene, region, and even time dependent. Future research should consider these factors in order to develop a comprehensive understanding of the immune response in males and females as these changes are likely the initiating agents that lead to the long-term, and often sex-specific, effects of early-life infection., (Published by Elsevier B.V.)

Easy-to-achieve interventions to promote healthy longevity are desired to diminish the incidence and severity of infections, as well as associated disability upon recovery. The dietary supplement palmitoylethanolamide (PEA) exerts anti-inflammatory and neuroprotective properties. Here, we investigated the effect of prophylactic PEA on the early immune response, clinical course, and survival of old mice after intracerebral E. coli K1 infection. Nineteen-month-old wild type mice were treated intraperitoneally with two doses of either 0.1 mg PEA/kg in 250 μl vehicle solution ( n = 19) or with 250 μl vehicle solution only as controls ( n = 19), 12 h and 30 min prior to intracerebral E. coli K1 infection. The intraperitoneal route was chosen to reduce distress in mice and to ensure exact dosing. Survival time, bacterial loads in cerebellum, blood, spleen, liver, and microglia counts and activation scores in the brain were evaluated. We measured the levels of IL-1β, IL-6, MIP-1α, and CXCL1 in cerebellum and spleen, as well as of bioactive lipids in serum in PEA- and vehicle-treated animals 24 h after infection. In the absence of antibiotic therapy, the median survival time of PEA-pre-treated infected mice was prolonged by 18 h compared to mice of the vehicle-pre-treated infected group ( P = 0.031). PEA prophylaxis delayed the onset of clinical symptoms ( P = 0.037). This protective effect was associated with lower bacterial loads in the spleen, liver, and blood compared to those of vehicle-injected animals ( P ≤ 0.037). PEA-pre-treated animals showed diminished levels of pro-inflammatory cytokines and chemokines in spleen 24 h after infection, as well as reduced serum concentrations of arachidonic acid and of one of its metabolites, 20-hydroxyeicosatetraenoic acid. In the brain, prophylactic PEA tended to reduce bacterial titers and attenuated microglial activation in aged infected animals ( P = 0.042). Our findings suggest that prophylactic PEA can counteract infection associated detrimental responses in old animals. Accordingly, PEA treatment slowed the onset of infection symptoms and prolonged the survival of old infected mice. In a clinical setting, prophylactic administration of PEA might extend the potential therapeutic window where antibiotic therapy can be initiated to rescue elderly patients.

Invasive meningococcal disease (IMD) caused by the serogroup W (MenW) sequence type-11 complex strain has recently emerged worldwide. Meningococcal infections due to this strain are associated with high case fatality and often atypical clinical manifestations. However, the annual IMD incidence was low, and MenW is rare in Japan. We described the first Japanese case of meningococcal meningitis and meningococcemia caused by this strain in a previously healthy 27-year-old woman. This case showed various neurological complications such as abducens palsy, cerebellitis, and cerebellar infarction, and reactive arthritis. This case provides useful information on the possibility of spreading IMD strains and the cause of various complications., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Bacillus Calmette-Guérin (BCG) is a live, attenuated strain of Mycobacterium bovis that is used to treat superficial bladder cancer. Although its use is typically associated with only mild, localized side effects, rare systemic complications can occur. Disseminated mycobacterium infections after BCG therapy have been reported in over 30 cases; however, central nervous system (CNS) infections do not commonly occur. We report a 74-year-old male who developed a M. bovis cerebellar abscess after receiving intravesical BCG infusion for bladder cancer for less than 1 year. This patient was successfully treated with antituberculosis therapy and corticosteroids. This patient case demonstrates that early-onset M bovis CNS infections can occur after BCG therapy. Patients presenting with altered mental status while on BCG therapy should be evaluated for disseminated infections.

Epsilon toxin (ET) is produced by Clostridium perfringens types B and D and causes severe neurological disorders in animals. ET has been observed binding to white matter, suggesting that it may target oligodendrocytes. In primary cultures containing oligodendrocytes and astrocytes, we found that ET (10(-9) M and 10(-7) M) binds to oligodendrocytes, but not to astrocytes. ET induces an increase in extracellular glutamate, and produces oscillations of intracellular Ca(2+) concentration in oligodendrocytes. These effects occurred without any change in the transmembrane resistance of oligodendrocytes, underlining that ET acts through a pore-independent mechanism. Pharmacological investigations revealed that the Ca(2+) oscillations are caused by the ET-induced rise in extracellular glutamate concentration. Indeed, the blockade of metabotropic glutamate receptors type 1 (mGluR1) prevented ET-induced Ca(2+) signals. Activation of the N-methyl-D-aspartate receptor (NMDA-R) is also involved, but to a lesser extent. Oligodendrocytes are responsible for myelinating neuronal axons. Using organotypic cultures of cerebellar slices, we found that ET induced the demyelination of Purkinje cell axons within 24 h. As this effect was suppressed by antagonizing mGluR1 and NMDA-R, demyelination is therefore caused by the initial ET-induced rise in extracellular glutamate concentration. This study reveals the novel possibility that ET can act on oligodendrocytes, thereby causing demyelination. Moreover, it suggests that for certain cell types such as oligodendrocytes, ET can act without forming pores, namely through the activation of an undefined receptor-mediated pathway., (© 2014 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd.)

Background: Palmitoylethanolamide (PEA), an endogenous lipid and a congener of anandamide, possesses a wide range of effects related to metabolic and cellular homeostasis including anti-inflammatory and neuroprotective properties., Methods: In vitro, we studied the ability of macrophages to phagocytose Escherichia coli K1 after stimulation with increasing doses of PEA. In vivo, wild-type mice were treated with PEA intraperitoneally 12 hours and 30 minutes before infection. Meningoencephalitis or sepsis was induced by intracerebral or intraperitoneal infection with E. coli K1., Results: Stimulation of macrophages with PEA for 30 minutes increased the phagocytosis of E. coli K1 without inducing the release of TNFα or CXCL1. Intracellular killing of E. coli K1 was higher in PEA-stimulated than in unstimulated peritoneal macrophages and microglial cells. Pre-treatment with PEA significantly increased survival of mice challenged intracerebrally or intraperitoneally with E. coli K1. This effect was associated with a decreased production of CXCL1, IL-1β and IL-6 in homogenates of spleen and cerebellum in mice treated with PEA., Conclusions: Our observations suggest that these protective effects of PEA in mice can increase the resistance to bacterial infections without the hazard of collateral damage by excessive stimulation of phagocytes.

Central nervous system (CNS) infections in ruminant livestock, such as listeriosis, are of major concern for veterinary and public health. To date, no host-specific in vitro models for ruminant CNS infections are available. Here, we established and evaluated the suitability of organotypic brain-slices of ruminant origin as in vitro model to study mechanisms of Listeria monocytogenes CNS infection. Ruminants are frequently affected by fatal listeric rhombencephalitis that closely resembles the same condition occurring in humans. Better insight into host-pathogen interactions in ruminants is therefore of interest, not only from a veterinary but also from a public health perspective. Brains were obtained at the slaughterhouse, and hippocampal and cerebellar brain-slices were cultured up to 49 days. Viability as well as the composition of cell populations was assessed weekly. Viable neurons, astrocytes, microglia and oligodendrocytes were observed up to 49 days in vitro. Slice cultures were infected with L. monocytogenes, and infection kinetics were monitored. Infected brain cells were identified by double immunofluorescence, and results were compared to natural cases of listeric rhombencephalitis. Similar to the natural infection, infected brain-slices showed focal replication of L. monocytogenes and bacteria were predominantly observed in microglia, but also in astrocytes, and associated with axons. These results demonstrate that organotypic brain-slice cultures of bovine origin survive for extended periods and can be infected easily with L. monocytogenes. Therefore, they are a suitable model to study aspects of host-pathogen interaction in listeric encephalitis and potentially in other neuroinfectious diseases., (© 2012 The Authors. International Journal of Experimental Pathology © 2012 International Journal of Experimental Pathology.)

Introduction: Cerebral aspergillosis is a rare and severe condition mostly affecting immunocompromised patients. The lesions are usually intra-axial and supratentorial; several radiologic patterns have been reported., Case Report: A 65-year-old patient with chronic lymphocytic leukemia presented with fever, headache, and a pontocerebellar syndrome. A brain magnetic resonance imaging (MRI) showed a ring-enhancing left pontocerebellar mass consistent with an infectious disease. Despite broad-spectrum antibiotic therapy, the patient worsened. A follow-up MRI examination disclosed a concomitant acute ischemic lesion in the ipsilateral thalamus and an irregular narrowing of the posterior cerebral artery close to the lesion. A retrospective analysis of the first MRI revealed a small mesencephalic ischemic lesion, contiguous to the extra-axial pontocerebellar mass. At surgical inspection the mass was found to be an extra-axial granuloma, with purulent components, attached to the petrous-tentorial angle, surrounded by a thick capsule. The lesion was only partially removed because of the tight relationship with the leptomeninges of the brain stem. Cerebral aspergillosis was the final histologic and microbiological diagnosis., Conclusion: In immunocompromised patients, the coexistence of an infectious lesion with involvement of contiguous vessels and consequent ischemic infarction should raise the suspicion of aspergillosis, even in unusual locations such as the pontocerebellar angle.

Purpose: To analyze the clinical characteristics and therapeutic outcome of patients with solely cerebellar bacterial brain abscess (BBA)., Case Report: Eight patients with solely cerebellar BBA, collected during a period of 23 years from 210 BBA patients, were included in this study. The eight patients were five men and three women, aged 5-54 years (mean, 36.6 years). Six of them were adults, one was a child, and one was an adolescent. Six patients had underlying medical/surgical problems. Of the clinical presentations, dizziness was the most common (87.5%, 7/8), followed by headache (62.5%, 5/8), altered consciousness (62.5%, 5/8), fever (50%, 4/8), ataxia (25%, 2/8), hearing impairment (12.5%, 1/8), dysarthria (12.5%, 1/8), and hemiparesis (12.5%, 1/8). The Image Severity Index (ISI) scores of these eight patients ranged from 6 to 12 points. All eight patients received both medical and surgical treatment. One patient died owing to a complication in the neurosurgical procedure and the remaining patients survived. The therapeutic outcome was quantified one month after discharge by modified Rankin scale (mRS) and the result showed six of the seven survivors had good outcomes, while the other one had a poor outcome (ataxic gait)., Conclusion: Cerebellar BBA accounted for 3.8% (8/210) of the overall BBA. In cerebellar BBA, dizziness is a frequent symptom. Early diagnosis and a combination of antimicrobial and neurosurgical intervention is important for its treatment. The small case number is a limitation of this study; therefore, further large-scale study of cerebellar BBA is needed for better delineation of the clinical characteristics, therapeutic outcome, and prognostic factors.

A necropsy was performed on a captive-born, 10-yr-old male Atlantic bottlenose dolphin (Tursiops truncatus) after it died acutely. Gross necropsy findings revealed hemorrhage within the right cerebrum, right cerebellum, and right eye. Histopathologic findings revealed a moderate multifocal acute necrotizing meningoencephalitis with intralesional fungal hyphae. Several pieces of cerebrum and cerebellum and cerebrospinal fluid were sent to the Fungus Testing Laboratory in San Antonio, Texas (U.S.A.). The culture yielded Fusarium oxysporum, which was confirmed by internal transcribed spacer and D1-D2 sequencing. Fusarium oxysporum infection has been reported in marine mammals. No cases of noncutaneous F. oxysporum infection in a cetacean that was not on long-term antimicrobials have been reported in the literature.

We report a 13-year-old girl with a hydatid cyst located in the posterior fossa. The pre-operative diagnosis was a cerebellar tumour; the cyst was operated on using puncture, aspiration, irrigation and resection. Sixteen months post-operatively, the patient is in a good health. A hydatid cyst must always be considered in the differential diagnosis of cystic lesions of the cranium, especially for those children living in rural areas.

Nocardia spp. infections in mammals cause pyogranulomatous lesions in a variety of organs, most typically the lung. Members of the Nocardia asteroides complex are the most frequently recognized pathogens. Nine cases of nocardiosis in free-ranging pinnipeds and 10 cases of nocardiosis in cetaceans were evaluated. Host species included the hooded seal (Cystophora cristata, n = 8), leopard seal (Hydrurga leptonyx, n = 1), Atlantic bottlenose dolphin (Tursiops truncatus, n = 4), beluga whale (Delphinapterus leucas, n = 4), and killer whale (Orcinus orca, n = 2). The most common presentation of nocardiosis in both pinnipeds and cetaceans was the systemic form, involving 2 or more organs. Organs most frequently affected were lung and thoracic lymph nodes in 7 of 9 cases in pinnipeds and 8 of 10 cases in cetaceans. Molecular identification and bacterial isolation demonstrated a variety of pathogenic species. N. asteroides, N. farcinica, N. brasiliensis, and N. otitisdiscaviarum are pathogenic for pinnipeds. In cetaceans N. asteroides, N. farcinica, N. brasiliensis, N. cyriacigeorgica, and N. levis are pathogenic. Hematoxylin and eosin and acid fast staining failed to reveal bacteria in every case, whereas modified acid fast and Grocott's methenamine silver consistently demonstrated the characteristic organisms. In both pinnipeds and cetaceans, juvenile animals were affected more often than adults. Hooded seals demonstrated more cases of nocardiosis than other pinnipeds.

A case of childhood enteric fever complicated by transient dysautonomia and cerebellitis is reported. The child was treated with intravenous antibiotics, and the complications were managed conservatively. Dysautonomia and cerebellitis resolved by day 5 and day 8 after admission, respectively. Results of a neurologic examination at the end of 6 months were normal. Dysautonomia complicating the course of childhood enteric fever is previously unreported.

Object: Cerebellar abscesses are common neurosurgical emergencies in developing countries, and have a distressingly high mortality rate of 10 to 15% even today. There is still no consensus on the standard approach to these lesions, and controversy persists over whether these lesions should be treated with primary excision or aspiration., Methods: The authors retrospectively analyzed 82 cases of cerebellar pyogenic abscesses in children treated at their institution over a period of 10 years. This represents the largest such series being described in literature. All lesions except 1 were otogenic in origin. The clinical and radiological features are discussed., Results: Primary excision was undertaken in 66 patients (80%) and aspiration in 16 patients (20%). Five patients in whom the abscesses were initially treated with aspiration subsequently underwent elective excision. Nine (12.6%) of 71 patients in whom the abscesses were excised had residual abscesses on postoperative imaging; in those who had undergone aspiration as the primary treatment, 6 (54.5%) of 11 patients had recurrent abscesses. There were no deaths among the patients who underwent excision of the abscess. Also, excision of posterior fossa abscesses required fewer repeated procedures with lower recurrence rates, and statistically lower rate of complications., Conclusions: Compared to primary aspiration, the authors found that primary excision is the preferred method for treating cerebellar abscesses.

Lyme disease is a multisystem infectious disease caused by the tick-borne spirochete, Borrelia burgdorferi. Central nervous system (CNS) involvement typically causes local inflammation, most commonly meningitis, but rarely parenchymal brain involvement. We describe a patient who presented with clinical findings suggesting a brainstem process. Magnetic resonance imaging (MRI) and positron emission tomography (PET) suggested a brainstem neoplasm. Prior to biopsy, laboratory evaluation led to the diagnosis of Lyme disease. Clinical and imaging abnormalities improved markedly following antimicrobial therapy. We describe Lyme disease involvement of the cerebellar peduncles with hypermetabolism on PET. Although MRI is the primary imaging modality for most suspected CNS pathology, the practical applications of PET continue to expand.

A wide spectrum of pathomorphological changes in the brain was revealed. They reflect various periods of cryptococcal infection under various conditions of immunodeficiency. In cases of brain cryptococcosis in HIV-infection, a significant spread of necrotic changes was noted. The dependence of structural changes severity in the brain on the size of fungal burden is found. It is shown that the disturbance of structural integrity of microvessel wall, its destruction under the influence of cryptococci is a major factor causing penetration of this infection directly into the substance of the brain.

We experienced two cases of brain abscess secondary to middle ear cholesteatoma. One, a 61-year-old woman, presented with left otalgia, appetite loss and nausea. The computed tomography obtained on admission revealed a middle ear cholesteatoma. The magnetic resonance image showed the presence of a brain abscess in the cerebellum. The brain abscess was drained and the cholesteatoma was removed using the canal down procedure under general anesthesia. Part of the cholesteatoma invaded the posterior cranial fossa was could not be removed from the otological surgical field. The patient has been under observation as an outpatient for 6 months already and no abnormal signs have been detected. The other patient, a 55-year-old man, was admitted to our hospital for a detailed examination because he had right otalgia and progressive headache. The examination of spinal fluid obtained by lumbar puncture showed marked elevation of the white blood cells count. Computed tomography revealed a middle ear cholesteatoma. The magnetic resonance image obtained on admission showed an area of low-intensity encapsulated by an area of high-intensity in the right temporal lobe. The abscess was drained and the cholesteatoma was removed using the canal down procedure under general anesthesia. The patient has been under observation for 1 year already and has presented no signs of recurrence.

Congenital dermal sinuses are tubular tracts which communicate the skin with deeper structures. It is a manifestation of defective separation of the ectoderm and neuroderm. The incidence is 1/2500-3000 births alive. Almost 10 % of congenital dermal sinuses are localized in the occipitocervical region. They are usually asymptomatic, unless an infectious process is concurrent (meningitis, abscess). We are presenting the case of a 12 months girl with unnoticed cutaneous stigmata in the occipital region, who was admitted with a meningeal syndrome and secondary neurological impairment. She had a cerebellar abscess and was treated with decompression by puncture of the abscess and antibiotics. When infection was resolved, congenital dermal sinus was excised. Process solves without morbidity. We reviewed the clinical and therapeutic features in cases reported previously in the literature.

Nuclear factor-kappaB (NF-kappaB) is a critical regulator of many genes involved in the pathogenesis of bacterial meningitis. Recently, activation of NF-kappaB was shown to be a key event in the inflammatory host response and the development of intracranial complications during experimental pneumococcal meningitis. Since the p50 subunit of NF-kappaB lacks a transactivation domain and can therefore act as a transcriptional repressor, we investigated whether NF-kappaB1 (p50) exerts anti-inflammatory effects in pneumococcal meningitis. p50-deficient mice had higher cerebellar pneumococcal titers (10.06+/-0.47 vs. 8.51+/-1.06 log colony-forming units [cfu]/cerebellum), cerebrospinal fluid (CSF) leukocyte counts (11,475+/-2340 vs. 8444+/-1405 cells/microl) and brain concentrations of interleukin-1beta (125.9+/-50.3 vs. 58.5+/-52.2 pg/mg protein) than their wild-type littermates. With ceftriaxone therapy, none of the wild-type mice but 43% of the p50-deficient animals died. In conclusion, lack of NF-kappaB1 (p50) was associated with impaired bacterial clearing, enhanced inflammatory host response and increased mortality during pneumococcal meningitis.

Previous studies have shown that Pseudomonas fluorescens and its lipopolysaccharide (LPS) exert dose-related cytotoxic effects on neurons and glial cells. In the present work, we investigated the time course effect of P. fluorescens MF37 and its LPS on cultured rat cerebellar granule neurons. The kinetics of binding of P. fluorescens to cerebellar granule neurons is rapid and reaches a mean of 3 bacteria/cell after 5 h. As demonstrated by measurement of the concentration of nitrite in the culture medium, P. fluorescens induces a rapid stimulation (3 h) of the nitric oxide synthase (NOS) activity of the cells. In contrast, LPS extracted from P. fluorescens requires a long lag phase (24 h) before observation of an activation of NOS. Measurement of the membrane resting potential of granule neurons showed that within 3 h of incubation there was no difference of effect between the action of P. fluorescens and that of its endotoxin. Two complementary approaches allowed to demonstrate that P. fluorescens MF37 presents a rapid invasive behaviour suggesting a mobilisation of calcium in its early steps of action. The present study reveals that P. fluorescens induces the sequential activation of a constitutive calcium-dependent NOS and that of an inducible NOS activated by LPS. Our results also suggest that in P. fluorescens cytotoxicity and invasion are not mutually exclusive events.

Although the fetal inflammatory response syndrome seems crucial to the association between intrauterine infection and white matter disease in human preterm infants, the underlying mechanisms remain unclear. Using our previously described rabbit model of cerebral cell death in the white matter and hippocampus induced by intrauterine Escherichia coli infection, we investigated inflammatory and astroglial responses in placenta and brain tissues, in correlation with cell death distribution. Brains and placentas were studied 12, 24, or 48 h following intrauterine inoculation of E. coli or saline (groups G12, G24, and G48). Diffuse monocyte-macrophage infiltrates positive for inducible nitric oxide synthase (i-NOS) were significantly more marked in G24 and G48 placentas than in controls. In the G48 fetuses with both diffuse cell death and focal periventricular white matter cysts mimicking cystic periventricular leukomalacia, a strong rabbit macrophage and inducible nitric oxide synthase immunostaining was observed at the border of these cystic lesions. In contrast, in the fetuses with only diffuse and significant cell death, no inflammatory or astroglial responses were detected in the white matter or hippocampus. Cell death was accompanied by i-NOS immunostaining in the hippocampus but not the white matter. Hippocampal cells positive for i-NOS usually displayed a neuronal phenotype. In this model, focal white matter cysts are accompanied by a robust inflammatory response, and diffuse cell death, which may mimic the white matter and hippocampal damage seen in very and extremely pre-term infants, occur in the absence of a detectable brain inflammatory response.

Leptospiral culture, direct immunofluorescence, and the polymerase chain reaction (PCR) were used to detect leptospiral material in postmortem specimens collected from eight patients who died of leptospirosis. Diagnosis of leptospiral infection was based on clinical summary (premortem) and confirmed by serological analysis and/or culture of leptospires. Leptospiral culture was the least sensitive technique, yielding two isolates (3%) from 65 samples. Both isolates were from the aqueous humour and cerebrospinal fluid of the same patient. Direct immunofluorescence was of intermediate sensitivity for detection of leptospires, confirming the presence of leptospires in 11% (2 of 18) of tissue samples from three patients. PCR analysis was the most sensitive technique for detection of leptospiral material in tissue samples, being positive in 20% (11 of 56) of samples from eight patients. Both samples (cerebellum and liver) positive by immunofluorescence were also positive by PCR. The sensitivity of the PCR assay was 1-10 leptospires ml(-1) sample, and the assay was specific for Leptospira pathogenic species. Multi-system involvement was indicated based on successful amplification of leptospiral DNA from more than one tissue sample, which corroborated with the clinical and pathologic findings. The results suggest that in acute and/or fatal leptospirosis, the pathogenesis of the pathologic features are related to the presence of the organisms in the tissues. In conclusion, PCR combined with serology appears to be a useful tool for diagnosis of leptospirosis and may be invaluable in epidemiological studies.

Unlabelled: Mycobacterium avium-M. complex (MAC) has been linked to devastating respiratory and systemic illnesses in patients, especially in those who are immunosuppressed. The purpose of this study is to describe a case of isolated central nervous system (CNS) infection with MAC. This is a single case report of a patient with isolated intracranial mycobacterial infection., Setting: the patient was treated and the immunohistochemical investigations were undertaken at the National Institutes of Health in Bethesda, Maryland, USA., Intervention: the patient initially was treated with a cocktail of antimycobacterial medications. However, because his disease was refractory, he underwent a suboccipital craniotomy and evacuation of his cerebellar mass. The patient was determined to have a low production of interferon-gamma (INF-gamma) and tumor necrosis factor-alpha (TNF-alpha) when compared to normal values. Despite extensive radiographic imaging studies and biopsies, there was no evidence of another focus of MAC infection in this patient. We conclude that intracranial infectious lesions in patients such as ours should be treated with conventional systemic antibiotic regimens as the first-line of therapy. We suggest neurosurgical intervention in medically refractory cases of intracranial infections.

Heterologous expression of Toll-like receptor (TLR)2 and CD14 in Chinese hamster ovary fibroblasts was reported to confer responsiveness to pneumococcal peptidoglycan. The present study characterized the role of TLR2 in the host immune response and clinical course of pneumococcal meningitis. Pneumococcal infection of mice caused a significant increase in brain TLR2 mRNA expression at both 4 and 24 h postchallenge. Mice with a targeted disruption of the TLR2 gene (TLR2-/-) showed a moderate increase in disease severity, as evidenced by an aggravation of meningitis-induced intracranial complications, a more pronounced reduction in body weight and temperature, and a deterioration of motor impairment. These symptoms were associated with significantly higher cerebellar and blood bacterial titers. Brain expression of the complement inhibitor complement receptor-related protein y was significantly higher in infected TLR2-/- than in wild-type mice, while the expression of the meningitis-relevant inflammatory mediators IL-1beta, TNF-alpha, IL-6, macrophage-inflammatory protein (MIP)-2, inducible NO synthase, and C3 was similar in both genotypes. We first ectopically expressed single candidate receptors in HEK293 cells and then applied peritoneal macrophages from mice lacking TLR2 and/or functional TLR4 for further analysis. Overexpression of TLR2 and TLR4/MD-2 conferred activation of NF-kappaB in response to pneumococcal exposure. However, pneumococci-induced TNF-alpha release from peritoneal macrophages of wild-type and TLR2/functional TLR4/double-deficient mice did not differ. Thus, while TLR2 plays a significant role in vivo, yet undefined pattern recognition receptors contribute to the recognition of and initiation of the host immune defense toward Streptococcus pneumoniae infection.

Many recent reports of acute cerebellitis with a critical or potentially critical course have changed the conception of the disease from an acute cerebellar ataxia with a benign course to a notable disease entity with a heterogeneous pathogenesis. The most characteristic finding by magnetic resonance imaging is diffuse cortical swelling of the cerebellum, often complicated by hydrocephalus or tonsillar herniation. A timely assessment and appropriate choice of treatment, including surgical intervention when indicated, are key to improving the outcome of affected patients.

Cerebral phaeohyphomycosis caused by Cladophialophora bantiana, a dematiaceous fungus, is a rare disease. The majority of cases have been reported among immunocompetent patients; only 4 cases have been published that describe transplantation patients. The overall prognosis is poor. Surgical therapy in combination with chemotherapy with itraconazole is recommended. We report the case of a heart transplant recipient with cutaneous, cerebral, and lung manifestation of Cladophialophora bantiana who died despite surgical and systemic, high-dosage itraconazole treatment.

A case of aspergillosis in a broiler breeder flock having respiratory and nervous system problems caused by Aspergillus fumigatus and Aspergillus niger is documented. Dyspnea, hyperpnea, blindness, torticollis, lack of equilibrium, and stunting were observed clinically. On postmortem examination of the affected birds, white to yellow caseous nodules were observed on lungs, thoracic air sacs, eyes, and cerebellum. Histopathologic examination of lungs and cerebellum revealed classic granulomatous inflammation and cerebellar lesions, necrotic meningoencephalitis, respectively. No lesions were noted in the cerebrum histopathologically. Aspergillus hyphae were observed in stained sections prepared from lesioned organs. Fungal spores and branched septate hyphae were observed in direct microscopy. Aspergillus fumigatus and A. niger were isolated from the inoculations prepared from the suspensions of organs showing lesions.

In this paper we present a case of a diabetic patient with nocardial abscesses of cerebrum, cerebellum and the spinal cord. The present case is the first case in the literature of solitary intramedullary abscess in cervical spinal cord, causing tetraplegia. Nocardia asteroides grew in a culture of the abscess pus. After either surgical excision or drainage of lesions, a triple combination regimen of chemotherapy (amikacin, ceftriaxone and trimethoprim-sulfamethoxazole) was given, but the patient was lost in the postoperative period. This case gives suggestive evidence of an association between cervical spinal cord involvement and poor prognosis in CNS nocardiosis.

The role of non-spore-forming anaerobic microflora in development of otogenic cerebral and cerebellar abscesses was studied in 49 patients with brain abscesses. Microfloral study of the middle ear discharge and content of cerebral abscess demonstrates that at present the role of pathogenic pyogenic staphylococci, streptococci and other kinds of purulent infection is lower than that of previously unreported non-spore-forming anaerobs in the pus of otogenic brain abscesses. It means that urgent sanation of the primary focus and cerebral abscesses should be supplemented with targeted combined antibacterial conservative therapy.

During the past six years 623 cases of coenurosis (gid) in sheep have been treated surgically. Cysts were removed successfully from 573 of them (92 per cent) and 517 (83 per cent) were able to return to their flocks, although 36 showed no clinical improvement In 37 cases, the cyst could not be localised, and postmortem examinations showed that in nine cases the cyst was in the brainstem, and in 28 cases it was in the cerebellum. Fifty-six cases deteriorated gradually after surgery and in these cases more than one cyst was found postmortem. Thirteen cases died during surgery.

A young woman with fulminant pyogenic meningitis became quadriplegic, areflexic and flaccid due to herniation of the cerebellar tonsils and compression of the upper cervical cord. This state of spinal shock was associated with absent F-waves. Intracranial pressure was greatly elevated and there was an uncertain relationship of tonsillar descent to a preceding lumbar puncture. Partial recovery occurred over 2 years. Tonsillar herniation can cause flaccid quadriplegia that may be mistaken for critical illness polyneuropathy. This case demonstrates cervicomedullary infarction from compression, a mechanism that is more likely than the sometimes proposed infectious vasculitis of the upper cord., (Copyright 2000 Harcourt Publishers Ltd.)

Our objective was to determine if suckling neonatal piglets are susceptible to enterohemorrhagic Escherichia coli (EHEC) O157:H7 disease. Surprisingly, EHEC O157:H7 caused more-rapid and more-severe neurological disease in suckling neonates than in those fed an artificial diet. Shiga toxin-negative O157:H7 did not cause neurological disease but colonized and caused attaching-and-effacing intestinal lesions.

Introduction: The clinical picture of lateral sinus thrombosis (LST) has changed with the advent of antibiotics, as have the utility of various diagnostic tests. LST may appear in children as a complication of acute otitis media, but nowadays it is more frequently encountered in adults with long-standing chronic ear disease., Method: A retrospective study of all the pediatric patients with LST between 1982 and 1997., Results: Thirteen cases of LST were diagnosed and treated by our department. In six cases, LST was due to acute otitis media and in the remaining cases it was due to chronic otitis media. Headache, fever, aural discharge and mastoid tenderness were the most frequent findings in these patients and four patients were initially diagnosed with meningitis. In the majority of the patients, LST was accompanied with other intracranial complications, such as perisinus abscess, brain abscess and meningitis. One patient with multiple brain abscesses, unresponsive to several drainage procedures, died. The other patients recovered and have since been followed-up as out-patients., Conclusion: LST may be difficult to diagnose due to previous antibiotic treatment and to the overlap of clinical findings with other entities such as meningitis. Despite the value of modern imaging techniques in the investigation of the disease, a high index of suspicion based on the clinical picture is warranted. Our results are consistent with those of other recent studies, who found that mortality of LST has dropped below 10%.

We report a childhood case of severe acute cerebellitis caused by Coxiella burnetii. After 10 days of fever and headache, the patient fell into a drowsy state. Examination of the cerebrospinal fluid (CSF) revealed pleocytosis, an increased level of protein, and negative results in bacterial and viral studies. Magnetic resonance imaging demonstrated a herniated tonsil compressed by the swollen vermis. Administration of minocycline relieved the patient's clinical symptoms. C. burnetii was isolated from the CSF obtained during convalescence.