First case of Arthrographis kalrae ethmoid sinusitis and ophthalmitis in the People's Republic of China

We present here the first case in the People's Republic of China of human disease caused by the fungus Arthrographis kalrae. The male patient had fungal panophthalmitis and invasive sinusitis involving the maxillary and ethmoid sinuses. He was an apparently healthy man before receiving trauma to his left eye. He complained of pain and loss of visual acuity in the injured eye, which displayed redness and edema and eventually discharged pus. His symptoms became more severe after he was treated with steroids and several antibacterial agents. A computed tomography scan of the left eye revealed that the maxillary and ethmoid sinuses were involved. A smear of purulent material from the left eye orbit revealed fungal elements, and cultures of the material grew a fungus. The isolate was identified as A. kalrae based on gross and microscopic morphologies, biochemical assays, and DNA sequence analysis. The patient received amphotericin B intravenously, itraconazole orally, and atomized allitridum by nebulizing allitridum therapy. The patient's wound healed following surgical intervention, but the patient lost the use of his left eye. This case should remind ophthalmologists and other clinicians to consider the possibility of infections being fungal when antibacterial agents have no effect and the patient's condition worsens.     

Aspergillus quadrilineatus, a new causative agent of fungal sinusitis.

Aspergillus quadrilineatus was found to be the etiologic agent of pansinusitis in a patient suffering from acute nonlymphoblastic leukemia and who had undergone allogeneic bone marrow transplantation. A. quadrilineatus was cultured from biopsy specimens of the maxillary sinus, and tissue sections with fungal stains showed a necrotic area containing dichotomously branching septate hyphae, which is morphologically consistent with Aspergillus species. The patient was successfully treated with a combination of surgical debridement, granulocyte transfusions, and intravenous administration of amphotericin B-cholesterol sulfate colloidal dispersion. This is the first report of an infection caused by A. quadrilineatus.     

Use of cerebrospinal fluid lactic acid concentration in the diagnosis of fungal meningitis

A patient with a several year history of normal pressure hydrocephalus was found to have an infection owing to Cryptococcus neoformans. Cryptococcal infection was not suspected until typical cells were observed in a Wright's stained smear of cerebrospinal fluid (CSF). A review of past medical findings in this patient showed elevated CSF values for lactic acid and protein. This case prompted us to review the use of lactic acid as an indicator of fungal meningitis and compare it to other more commonly used nonspecific indicators of fungal meningitis, notably the concentrations of glucose and protein, and the number of leukocytes in CSF. In our institution, all 10 culturally proven cases of fungal meningitis, for which the lactic acid concentration in the CSF was available, were found to have an elevated lactic acid concentration (range 3.2 to 13.3 mmol per L vs normal range 0.8 to 2.8 mmol per L). No other nonspecific indicator was elevated in all 10 patients. In view of the poor sensitivity of stained smear or wet preparations and cultures, when less than five ml of CSF are used for culture, an elevated lactic acid value in a patient with or without signs of meningitis should raise the suspicion of fungal infection.     

Usefulness of Fungiflora Y to detect fungus in a frozen section of allergic mucin

Allergic fungal sinusitis is a non-invasive disease characterized by pansinusitis with nasal polyps, with most causative agents being members of the dematiaceous fungi. Reported herein is the ninth Japanese case of allergic fungal sinusitis; an Alternaria species was culturally identified as the etiological agent. The present patient, a 32-year-old man, presented with multiple sinusitis and nasal polyps. Allergic mucin, which is a histological hallmark of this disease, was examined intraoperatively on frozen section. Although characteristic histology, including laminated masses of mucin and aggregates of eosinophils, was seen in HE-stained sections, fungal hyphae were scarce and recognized merely as clear spaces. Because fluorescent stilbene derivatives seem useful for the rapid detection of fungi, Fungiflora Y, a commercially available staining kit that includes a fluorescent stilbene derivative, was applied to the sections, and hyphae were successfully visualized using a fluorescence microscope. This stain takes only several minutes to perform. It is concluded that Fungiflora Y should be used when fungal elements are hard to find on HE stain, especially in cases in which rapid detection of fungus is requested.     

Visual attention deficits in Alzheimer's disease: an fMRI study

Cognitive and neuroscience studies indicate that attentional operations are impaired in Alzheimer's disease (AD). Our goal was to define the anatomical areas of activation associated with visual attention processing and to define deficits or changes that may occur in AD patients compared with control group. Thirteen AD patients and 13 age- and education-matched normal controls were tested in two visual search tasks (one was a conjunction task, where feature binding is required. The other was a subset task, where group stimuli is needed without feature binding) using fMRI techniques. After stereotactical normalization, voxel-by-voxel t statistics was used to compare activated brain areas between patients and control subjects. Our findings suggest that both search tasks are controlled by partially overlapping cerebral networks, including parietal, frontal and occipital-temporal cortical regions and primary visual cortex. The AD patient group showed less activation in both parietal lobes and the left frontal regions, while increased activation was found in the right frontal lobes and the right occipito-temporal cortical regions with the conjunction task. In the subset task, decreased activation in AD patients was seen in the left parietal lobe and bilateral frontal lobes, while increased activation was seen in both medial temporal lobes. In addition, for the comparison between tasks, The difference is very small for AD patients. Control group showed a higher amplitude in the right prefrontal region, temporal cortical regions and parietal lobe. These results indicate that attention deficits in AD patients may be attributed to both binding problem and grouping inefficiency.     

Fatal-stroke syndrome revealing fungal cerebral vasculitis due to Arthrographis kalrae in an immunocompetent patient

We report an uncommon clinical presentation of a unique case of fatal invasive fungal cerebral vasculitis due to Arthrographis kalrae in a nonimmunocompromised host. The identity of the fungus was determined by morphological characteristics and by analysis of internal transcribed spacer 1 sequences and was confirmed by postmortem examination of the brain tissues. Establishing rapidly the link between the clinical syndromes and the fungal infection of the central nervous system is essential to improve the outcome. As our case has shown, it is more challenging to make a diagnosis of fungal infection when there are no risk factors of immunodeficiency and when the clinical presentation seems uncommon.     

Primary gastrointestinal mucormycosis in an immunocompetent person

In the past decade, mucormycosis has emerged as an important lethal infection in diabetics and other immunocompromised hosts. Rhinosinusitis, pansinusitis, rhino-orbital and rhinocerebral are the common classical manifestations of mucormycosis. However, primary gastrointestinal (GI) mucormycosis is an uncommon disease associated with a high mortality rate. Stomach is the most common site involved in GI mucormycosis. Reported cases of GI mucormycosis in an immunocompetent host are very few in the literature. Here we present a case of a young male with fungal sepsis secondary to GI mucormycosis in an immunocompetent person.     

Exserohilum rostratum: Anatomy of a national outbreak of fungal meningitis

On 18 September 2012, an alert physician caring for a patient with fungal meningitis who had received an epidural methylprednisolone acetate injection approximately 6 weeks earlier, recognized its possible significance and reported this case to the Tennessee Department of Health, who in turn notified the Centers for Disease Control and Prevention. Shortly thereafter, additional cases of fungal meningitis were reported, and so began a large, unprecedented, multistate fungal meningitis outbreak. The predominant etiologic agent was Exserohilum rostratum, a black mould that was not known to have previously caused an outbreak of such devastating disease of this magnitude. The contaminated medication was prepared and distributed by a compounding pharmacy located in Massachusetts. This article reviews (i) the development and handling of the outbreak; (ii) the clinical manifestations and management of the infections; (iii) the detection, identification, and characteristics of E. rostratum, including the factors that might enhance its virulence; (iv) the regulatory concerns for microbiological quality control; and (v) what we have learned from this experience.     

Cryptococcal meningitis in immunocompetent patients

Five cases of cryptococcal meningitis (CM) in immunocompetent patients who were initially diagnosed as either tuberculous meningitis or partially treated pyogenic meningitis are presented. There were 3 male and 2 female patients in the age range of 21 to 42 years. These patients presented as subacute meningitis. Additional features were visual impairment (4 cases), papilloedema (3 cases), sixth cranial nerve palsy (3 cases) and ataxic hemiparesis (one case). There was a mediastinal mass of fungal aetiology in one patient. While routine analysis of CSF showed a variable picture, it is the India ink preparation, test for cryptococcal antigen and culture for fungus which gave the diagnosis. These patients were treated with standard antifungal therapy. While one patient died and one patient recovered completely, three other patients were left with permanent visual impairment. It is concluded that CM is uncommon but an important cause of non-acute meningitis and should be included in the list of causes of preventable blindness.     

Prevalence of fungal meningitis among HIV positive & negative subjects in Indore (MP state)

The aim of the study was to find out the prevalence of fungal meningitis among AIDS cases and to assess the prognosis of fungal meningitis among HIV positive & negative subjects. The study comprised of 15 & 10 cases of fungal meningitis among HIV positive & negative subjects respectively during the study period 1992-2001. India ink preparation and Gram's staining procedures were carried out on the centrifuged CSF deposits. The CSF deposits were also used for bacterial and fungal culture. In the present study the prevalence of fungal meningitis was noted among 15 (3.1%) of 483 AIDS cases. Twelve of them had cryptococcal meningitis while 3 were infected with Candida albicans. Four AIDS cases presented fungal meningitis as a primary opportunistic infection and HIV status was confirmed in 4 of them after the diagnosis of fungal meningitis. 13 of the 15 cases were in the age group 26-40 yrs while one was 55 yrs old and the other 16 month old child; these two cases had blood transfusion transmitted and vertically transmitted mode of HIV transmission respectively. Further, only two of 15 cases were females and both acquired HIV infection through blood transfusion. Overall prognosis of fungal meningitis was poor among HIV positives and 7 of the 15 cases died in hospital within 2-3 weeks after diagnosis of cryptococcal meningitis. Among HIV negative subjects, ten cases of fungal meningitis (3 with Candida albicans and 7 with Cryptococcous neoformans) were noted at our end and nine of them had immunocompromised status (3 cases of renal transplant on immunosuppressives, 3 cases neonates/infant and 2 diabetic subjects. The fungal meningitis is one of the important causes of morbidity & mortality among immunocompromised among HIV positive subjects.     

Sinusite fongique allergique à Curvularia lunata

We report the case of a 28-year-old caucasian female living in French Guyana. For 2 years she had been complaining of unilateral nasal obstruction with anosmia. A CT scan of the sinuses showed unilateral pansinusitis with polyps and lysis of the sphenoid bone. Histological examination of mucus showed polynuclear eosinophil cells with Charcot-leyden crystals and fungal hyphae. No fungal invasion was observed in the sub-mucosa. Mycological examination of mucus showed septated fungal hyphae identified as Curvularia lunata by culture. Treatment consisted in unilateral ethmoidectomy with sphenoidotomy combined with a short local corticotherapy.     

Cerebrospinal fluid hepatocyte growth factor level in meningitis

BACKGROUND AND PURPOSE: Hepatocyte growth factor (HGF) is a multifunctional cytokine that has been found to be elevated in tuberculous and bacterial meningitis, but no evaluation has been undertaken of its usefulness in identifying various forms of aseptic meningitis. METHODS: In a retrospective study, the levels of HGF in the cerebrospinal fluid of 65 patients were measured prior to treatment. The association of HGF with non-infectious diseases and clinically or microbiologically proven bacterial, tuberculous, viral, fungal and parasitic meningitis was observed, along with its relation to other parameters of the cerebrospinal fluid. RESULTS: Forty six of the 65 patients (71%) were diagnosed as having meningitis. Cerebospinal fluid HGF level was significantly elevated in patients with meningitis compared with patients with non-infectious diseases (1501 vs 578 pg/mL; Mann-Whitney U test, p=0.001). The highest HGF level was found in bacterial meningitis (2699 pg/mL), followed by tuberculous meningitis (1540 pg/mL), viral meningitis (1431 pg/mL), fungal meningitis (714 pg/mL) and parasitic meningitis (174 pg/mL). There was no association between HGF level and other parameters of the cerebrospinal fluid (Pearson's correlation test). CONCLUSION: Cerebrospinal fluid HGF may offer additional information in the classification of meningitis. This may assist in patient management when no pathogen is cultured from the cerebrospinal fluid and when other parameters of the cerebrospinal fluid demonstrate equivocal results.     

Frontal asymmetry in behavioral variant frontotemporal dementia: clinicoimaging and pathogenetic correlates

We aimed to assess associations between clinical, imaging, pathologic, and genetic features and frontal lobe asymmetry in behavioral variant frontotemporal dementia (bvFTD). Volumes of the left and right dorsolateral, medial, and orbital frontal lobes were measured in 80 bvFTD subjects and subjects were classified into 3 groups according to the degree of asymmetry (asymmetric left, asymmetric right, symmetric) using cluster analysis. The majority of subjects were symmetric (65%), with 20% asymmetric left and 15% asymmetric right. There were no clinical differences across groups, although there was a trend for greater behavioral dyscontrol in right asymmetric compared with left asymmetric subjects. More widespread atrophy involving the parietal lobe was observed in the symmetric group. Genetic features differed across groups with symmetric frontal lobes associated with C9ORF72 and tau mutations, while asymmetric frontal lobes were associated with progranulin mutations. These findings therefore suggest that neuroanatomical patterns of frontal lobe atrophy in bvFTD are influenced by specific gene mutations.     

(1,3)-β-d-Glucan in Cerebrospinal Fluid for Diagnosis of Fungal Meningitis Associated with Contaminated Methylprednisolone Injections

Prompt diagnosis and treatment of fungal meningitis are critical, but culture is insensitive. (1,3)-β-d-Glucan (BDG) testing is FDA approved for serological diagnosis of invasive fungal disease; however, BDG testing is not approved for cerebrospinal fluid (CSF), and the appropriate cutoff value is unknown. We aimed to validate the diagnostic accuracy of CSF BDG measurements for fungal meningitis among patients exposed to contaminated methylprednisolone acetate (MPA). A retrospective observational study was conducted at St. Joseph Mercy Hospital and Vanderbilt University from November 2013 to February 2014. Patients were included if they had received a contaminated MPA injection. Cases were classified as probable or proven meningitis according to Centers for Disease Control and Prevention guidelines. CSF BDG testing was performed according to the package insert instructions for serum samples, and results were validated using Clinical and Laboratory Standards Institute procedures (MiraVista Diagnostics). Of 233 patients, 45 had meningitis (28 proven cases), 53 had spinal/paraspinal infections (19 proven cases), and 135 did not develop disease. Using the manufacturer''s cutoff value (≥80 pg/ml), the sensitivity and specificity were 96% and 95%, respectively, for proven meningitis and 84% and 95% for probable or proven meningitis. Receiver operating characteristic analysis identified the optimal cutoff value for proven meningitis to be 66 pg/ml (sensitivity, 100%; specificity, 94%) and that for probable or proven meningitis to be 66 pg/ml (sensitivity, 91%; specificity, 92%). Our results suggest that CSF BDG measurements are highly sensitive and specific for the diagnosis of fungal meningitis associated with contaminated MPA injections. Further study on the utility of CSF BDG testing for other types of fungal meningitis is needed.     

Age-related changes in word retrieval: role of bilateral frontal and subcortical networks

Healthy older adults frequently report word-finding difficulties, yet the underlying cause of these problems is not well understood. This study examined whether age-related changes in word retrieval are related to changes in areas of the frontal lobes thought to subserve word retrieval or changes in areas of the inferior temporal lobes thought to be involved in semantic knowledge. Twenty younger and 20 older healthy adults named aloud photographs during event-related fMRI. Results showed that in the face of equivalent naming accuracy, older adults activated a larger frontal network than younger adults during word retrieval, but there were no activity differences between groups in the fusiform gyrus, suggesting that the substrates for word retrieval but not for semantic knowledge change with aging. Additionally, correlations between BOLD response and naming accuracy and response latency were found in several frontal and subcortical regions in older adults. Findings are discussed in the context of possible compensatory mechanisms invoked to maintain performance in healthy aging, and suggest that increased involvement of the right hemisphere is not universally beneficial to performance.     

Hemispheric asymmetry and emotion: effects of nonverbal affective stimuli

The purpose of the present study was to investigate the cerebral processing of affect by measuring the electroencephalographic activity of the frontal lobes and electrodermal activity in response to a series of nonverbal affective stimuli. Cognitive and sensorimotor processes were minimized by employing a design that did not require subjects to perform any task other than attending to the stimuli. Summated frontal alpha activity was determined during nonemotional, positive, and negative stimuli. Changes in bilateral skin conductance were also measured during the presentation of the stimuli. Results demonstrated that there was bilateral activation of the frontal lobes in response to the positive affective stimuli. The level of activation of the frontal lobes was the same in response to both negative and nonemotional stimuli. There was no evidence of hemispheric asymmetry or gender-related differences in patterns of activation. Furthermore, there was no evidence of lateralization in the skin conductance response magnitude.     

Epileptogenic Networks in Two Patients with Hypothalamic Hamartoma

Hypothalamic hamartomas (HH) are typically associated with gelastic seizures but also implicated in the genesis of other seizure types. In order to identify networks involved in seizure generation, we performed EEG-fMRI in two adult patients with HH, the first with predominantly gelastic seizures and the second with complex partial and no typical gelastic seizures. The ictal and interictal analysis of the patient with gelastic seizures revealed the involvement of the HH, the cingulate gyrus, the precuneus and the prefrontal cortex. The interictal analysis of the patient with complex partial seizures, showed changes in blood oxygen-level dependent signal over the temporal lobes, the base of the frontal lobe, the cingulate, the precuneus and the prefrontal cortex, but not the HH. The differences in the neural networks implicated may account for differences in clinical manifestation of seizures owing to HH.     

Shape analysis of spatial relationships between orbito‐ocular and endocranial structures in modern humans and fossil hominids

The orbits and eyes of modern humans are situated directly below the frontal lobes and anterior to the temporal lobes. Contiguity between these orbital and cerebral elements could generate spatial constraints, and potentially lead to deformation of the eye and reduced visual acuity during development. In this shape analysis we evaluate whether and to what extent covariation exists between ocular morphology and the size and spatial position of the frontal and temporal areas in adult modern humans. Magnetic resonance imaging (MRI) was used to investigate patterns of variation among the brain and eyes, while computed tomography (CT) was used to compare cranial morphology in this anatomical region among modern humans, extinct hominids and chimpanzees. Seventeen landmarks and semi‐landmarks that capture the outline of the eye, frontal lobe, anterior fossa/orbital roof and the position of the temporal tips were sampled using lateral scout views in two dimensions, after projection of the average grayscale values of each hemisphere, with midsagittal and parasagittal elements overlapped onto the same plane. MRI results demonstrated that eye position in adult humans varies most with regard to its horizontal distance from the temporal lobes and, secondly, in its vertical distance from the frontal lobes. Size was mainly found to covary with the distance between the eye and temporal lobes. Proximity to these cerebral lobes may generate spatial constraints, as some ocular deformation was observed. Considering the CT analysis, modern humans vary most with regard to the orientation of the orbits, while interspecific variation is mainly associated with separation between the orbits and endocranial elements. These findings suggest that size and position of the frontal and temporal lobes can affect eye and orbit morphology, though potential effects on eye shape require further study. In particular, possible effects of these spatial and allometric relationships on the eye and vision should be examined using ontogenetic samples, vision parameters such as refractive error in diopters, and three‐dimensional approaches that include measures of extraocular soft tissues within the orbit.     

Infective endocarditis caused by group G streptococcus with multiple cerebral emboli

The group G streptococcal endocarditis is a rare form of infective endocarditis. In this form of infective endocarditis, serious neurological complications most commonly develop. We reported this case because of its being an unusual form of infective endocarditis that was caused by Group G Streptococcus. We also reviewed the literature. The patient was admitted to infectious disease service with a presumptive diagnosis of central nervous system infection. Blood cultures were positive for group G streptococcus. There was a mass on the posterior surface of the mitral valve which was 2 x 2.5 cm in length on the echocardiography. In the cranial computerized tomography of our patient, slightly increased contrast media uptake was observed in the both parietal lobes, in the both frontal lobes, and in the anterior areas of right occipital lobe. Therefore, this case was assumed as infective endocarditis caused by group G streptococcus with multiple cerebral emboli. Ceftriaxone was given for 4 weeks and gentamicin was given for 2 weeks, and progressive improvement of the patient's condition was seen.     

Allergic Bipolaris sinusitis: clinical and immunopathologic characteristics

Allergic Aspergillus sinusitis was first reported in 1983. We present the first three cases of allergic fungal sinusitis caused by the black fungus Bipolaris spicifera. The patients were young, atopic, and immunocompetent. All three patients demonstrated pansinusitis with nasal polyps and underwent multiple surgical procedures. Pathologic features included a characteristic mucoid exudate containing eosinophils, Charcot-Leyden crystals, and fungal hyphae. In two cases there was bony erosion revealed by computed tomography scan but no histologic evidence of direct fungal invasion into the mucosa or bony trabeculae. Immunologic features, including total eosinophil count, total serum IgE, immediate and late-phase skin response to B. spicifera, serum precipitins, and specific IgE and IgG to B. spicifera, are described. B. spicifera is a previously unrecognized cause of allergic fungal sinusitis that may be an underdiagnosed disorder. This diagnosis should be considered in atopic patients with nasal polyps and pansinusitis unresponsive to conventional medical therapy. Diagnostic criteria include characteristic histologic allergic mucin, culture identification of fungus, positive immediate cutaneous reactivity to fungal extract, positive serum precipitins, and elevated specific IgE and IgG antibodies.