Protocolo de un día para la PET/TC con 18F-FDG y 13N-amonio con escala de desacoplamiento de la captación para diferenciar el glioma de bajo grado no tratado de la inflamación / One-day protocol for 18F-FDG and 13N-ammonia PET/CT with uptake decoupling score in differentiating untreated low-grade glioma from inflammation

PROPÓSITO: La identificación precisa de los gliomas de bajo grado (GBG; grados I y II de la Organización Mundial de la Salud) y su diferenciación de las lesiones por inflamación cerebral (BIL) sigue siendo difícil; sin embargo, es esencial para el tratamiento. Este estudio evaluó si un protocolo de un día para la PET/TC con 18F-FDG y 13N-amonio con análisis de desacoplamiento de la captación podría diferenciar los GBG de las BIL. MATERIALES Y MÉTODOS: Veintiocho pacientes con GBG y 16 pacientes con BIL se sometieron a PET/TC con 18F-FDG y 13N-amonio el mismo día antes de cualquier tipo de terapia. La puntuación de desacoplamiento y la relación tumor/tejido normal (T/N) de 18F-FDG y 13N-amonio se calcularon en cada localización. Se utilizó la prueba t de Student para comparar valores, y el análisis de la curva ROC para establecer un valor de corte para la relación T/N y la puntuación de desacoplamiento. Se calculó el área bajo la curva (AUC) para evaluar la eficacia diferencial. RESULTADOS: Se observaron diferencias significativas en la relación T/N de 13N-amonio (p = 0,018) y en la puntuación de desacoplamiento (p = 0,003) entre los GBG y las BIL; sin embargo, la relación T/N de 18F-FDG no mostró ninguna diferencia (p = 0,413). Los valores de corte óptimos para la relación T/N de 18F-FDG, la relación T/N de 13N-amonio y la puntuación de desacoplamiento fueron 0,73, 0,97 y 2,31, respectivamente, con AUC correspondientes de 0,48, 0,68 y 0,77. Los respectivos parámetros de sensibilidad, especificidad y precisión que utilizan estos valores de corte fueron 53,6%, 62,5% y 56,8%, respectivamente, para 18F-FDG; 50,0%, 75,0% y 59,1%, respectivamente, para 13N-amonio; y 60,7%, 93,8% y 72,7%, respectivamente, para la puntuación de desacoplamiento. CONCLUSIONES: La puntuación de desacoplamiento de la captación de 18F-FDG/13N amonio se puede utilizar para discriminar entre GBG y BIL. El uso de un mapa de desacoplamiento de estos dos trazadores puede mejorar el análisis visual y la precisión del diagnóstico

PURPOSE: Accurate identification of low-grade gliomas (LGGs; World Health Organization grades I and II) and their differentiation from brain inflammation lesions (BILs) remains difficult; however, it is essential for treatment. This study assessed whether a one-day protocol for voxel-wise 18F-FDG and 13N-ammonia PET/CT with uptake decoupling analysis could differentiate LGGs from BILs. MATERIALS AND METHODS: Twenty-eight patients with LGGs and 16 patients with BILs underwent 18F-FDG and 13N-ammonia PET/CT on the same day before any type of therapy. The decoupling score and tumor-to-normal tissue (T/N) ratio of 18F-FDG and 13N-ammonia were calculated at each location. Student's t-test was used to compare values, and ROC curve analysis was used to establish a cut-off value for the T/N ratio and decoupling score. Area under the curve (AUC) was calculated to evaluate differential efficacy. RESULTS: Significant differences were observed in 13N-ammonia T/N ratio (p = 0.018) and decoupling score (p = 0.003) between LGGs and BILs; however, the 18F-FDG T/N ratio did not show any differences (p = 0.413). Optimal cut-off values for 18F-FDG T/N ratio, 13N-ammonia T/N ratio, and decoupling score were 0.73, 0.97, and 2.31, respectively, with corresponding AUCs of 0.48, 0.68, and 0.77. The respective sensitivity, specificity, and accuracy parameters using these cut-off values were 53.6%, 62.5%, and 56.8%, respectively, for 18F-FDG; 50.0%, 75.0%, and 59.1%, respectively, for 13N-ammonia; and 60.7%, 93.8%, and 72.7%, respectively, for decoupling score. CONCLUSIONS: 18F-FDG/13N-ammonia uptake decoupling score can be used to discriminate between LGGs and BILs. Use of a decoupling map of these two tracers can improve visual analysis and diagnostic accuracy

One-day protocol for 18F-FDG and 13N-ammonia PET/CT with uptake decoupling score in differentiating untreated low-grade glioma from inflammation. / Protocolo de un día para la PET/TC con 18F-FDG y 13N-amonio con escala de desacoplamiento de la captación para diferenciar el glioma de bajo grado no tratado de la inflamación.

PURPOSE: Accurate identification of low-grade gliomas (LGGs; World Health Organization grades I and II) and their differentiation from brain inflammation lesions (BILs) remains difficult; however, it is essential for treatment. This study assessed whether a one-day protocol for voxel-wise 18F-FDG and 13N-ammonia PET/CT with uptake decoupling analysis could differentiate LGGs from BILs. MATERIALS AND METHODS: Twenty-eight patients with LGGs and 16 patients with BILs underwent 18F-FDG and 13N-ammonia PET/CT on the same day before any type of therapy. The decoupling score and tumor-to-normal tissue (T/N) ratio of 18F-FDG and 13N-ammonia were calculated at each location. Student's t-test was used to compare values, and ROC curve analysis was used to establish a cut-off value for the T/N ratio and decoupling score. Area under the curve (AUC) was calculated to evaluate differential efficacy. RESULTS: Significant differences were observed in 13N-ammonia T/N ratio (p=0.018) and decoupling score (p=0.003) between LGGs and BILs; however, the 18F-FDG T/N ratio did not show any differences (p=0.413). Optimal cut-off values for 18F-FDG T/N ratio, 13N-ammonia T/N ratio, and decoupling score were 0.73, 0.97, and 2.31, respectively, with corresponding AUCs of 0.48, 0.68, and 0.77. The respective sensitivity, specificity, and accuracy parameters using these cut-off values were 53.6%, 62.5%, and 56.8%, respectively, for 18F-FDG; 50.0%, 75.0%, and 59.1%, respectively, for 13N-ammonia; and 60.7%, 93.8%, and 72.7%, respectively, for decoupling score. CONCLUSIONS: 18F-FDG/13N-ammonia uptake decoupling score can be used to discriminate between LGGs and BILs. Use of a decoupling map of these two tracers can improve visual analysis and diagnostic accuracy.

Low Central Nervous System Posaconazole Concentrations during Cerebral Phaeohyphomycosis.

Posaconazole diffusion has been documented in various organs, which contrasts with the scarce data available for the human central nervous system (CNS). We analyzed posaconazole concentrations in plasma and multiple CNS specimens taken from a patient who received posaconazole because of cerebral phaeohyphomycosis. Low posaconazole concentrations were obtained in CNS specimens, with sample-to-plasma ratios between 5% and 22%. This case highlights the role of neurosurgery during cerebral phaeohyphomycoses, even those caused by posaconazole-susceptible black fungi.

Experimental Scedosporiosis Induces Cerebral Oedema Associated with Abscess regarding Aquaporin-4 and Nrf-2 Depletions.

Cerebral involvement especially brain abscess is life-threatening complication and major cause of death during Scedosporium apiospermum infection. However, little is known about pathogenesis of brain oedema associated with abscess in scedosporiosis. Experimental scedosporiosis was conducted in BALB/cMlac mice to characterize the presence of brain oedema, its type, and its related mechanisms focusing on aquaporin (AQP)-4, nuclear factor erythroid-2 related factor (Nrf-2), and tumor necrotic factor (TNF)-α. The results revealed that S. apiospermum infection induced severe inflammatory environment relevant to TNF-α expression and cytogenic oedema-associated brain abscess predominately in cerebrum of immunocompromised mice without voriconazole treatment reflecting to downregulation of AQP-4 in neighboring abscess areas and oedematous blood vessels. Downregulation of Nrf-2 in neuronal cells and myelin degeneration were significantly observed in nontreated mice. In summary, oxidative stress, severe inflammatory response, and space-occupying mass from abscess formation inducing tissue hypoxia might be the postulate causes of oedema induced by scedosporiosis.

Staphylococcus aureus infected embolic stroke upregulates Orm1 and Cxcl2 in a rat model of septic stroke pathology.

OBJECTIVE: Ischaemic brain lesions and brain abscesses are frequent in both human and animal cases of septic embolic stroke. However, existing models of brain infection do not reflect central aspects of septic embolic stroke. Our aim was to compare septic and non-septic embolic stroke in order to identify gene expressions, inflammatory mediators and brain damage in a rat model. METHODS: We created precisely located focal brain infarcts in a rat model of Staphylococcus aureus infected embolic stroke. To cause septic embolic stroke we used a fibrin-rich embolus with bacteria, while every rat in the control group received a non-infected embolus. 64 rats were randomized to receive sham-surgery, sterile embolic stroke or septic embolic stroke. All groups were compared for brain pathology, mortality, gene expressions and inflammatory mediators using histology and reverse transcription quantitative real-time PCR. RESULTS: Although infarct volumes did not differ, septic embolic stroke caused higher mortality than sterile embolic stroke (p=  0.002). Brain abscesses were observed only in the septic group. Approximately 400-500 fold increases were observed for Orm1 and Cxcl2 respectively (1.00E-08 < p < 1.92E-07) in the septic group compared to the sterile group, and these were the most dramatically regulated genes in septic embolic stroke compared to sterile embolic stroke. CONCLUSIONS: Septic embolic stroke caused brain abscesses, increased mortality and upregulated Orm1 and Cxcl2 gene expressions compared to non-infected embolic stroke. The dramatic Orm1 increase observed in the septic group is unprecedented and suggests a significant biological role of Orm1 during septic neuroinflammation.

Mycobacterium bovis Cerebellar Abscess Following Treatment With Bacillus Calmette-Guérin.

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.

Simultaneous detection of valine and lactate using MEGA-PRESS editing in pyogenic brain abscess.

Valine and lactate have been recognized as important metabolic markers to diagnose brain abscess by means of MRS. However, in vivo unambiguous detection and quantification is hampered by macromolecular contamination. In this work, MEGA-PRESS difference editing of valine and lactate is proposed. The method is validated in vitro and applied for quantitative in vivo experiments in one healthy subject and two brain abscess patients. It is demonstrated that with this technique the overlapping lipid signal can be reduced by more than an order of magnitude and thus the robustness of valine and lactate detection in vivo can be enhanced. Quantification of the two abscess MEGA-PRESS spectra yielded valine/lactate concentration ratios of 0.10 and 0.27. These ratios agreed with the concentration ratios determined from concomitantly acquired short-TE PRESS data and were in line with literature values. The quantification accuracy of lactate (as measured with Cramér-Rao lower bounds in LCModel processing) was better for MEGA-PRESS than for short-TE PRESS in all acquired in vivo datasets. The Cramér-Rao lower bounds of valine were only better for MEGA-PRESS in one of the two abscess cases, while in the other case coediting of isoleucine confounded the quantification in the MEGA-PRESS analysis. MEGA-PRESS and short-TE PRESS should be combined for unambiguous quantification of amino acids in abscess measurements. Simultaneous valine/lactate MEGA-PRESS editing might benefit the distinction of brain abscesses from tumors, and further categorization of bacteria with reasonable sensitivity and specificity.

Toxic levels of ammonia in human brain abscess.

OBJECTIVE: Brain abscesses could lead to cerebral symptoms through tissue destruction, edema, changes in brain architecture, and increased intracranial pressure. However, the possibility that the pus itself could contribute to symptoms has received little attention. Brain abscesses are areas of tissue destruction, proteolysis, and formation of free amino acids, which are energy substrates for bacteria and possible sources of ammonia. Ammonia is neurotoxic, may cause brain edema, and could contribute to the symptoms of brain abscesses. METHODS: The authors analyzed the extracellular phase of pus from 14 patients with brain abscesses with respect to ammonia and amino acids. For comparison, CSF from 10 patients undergoing external ventricular drainage was included. The ammonia-forming ability of Streptococcus intermedius and Staphylococcus aureus, two common microbial isolates in brain abscesses, was studied in vitro. RESULTS: In brain abscesses ammonia was 15.5 mmol/L (median value; range 1.7-69.2 mmol/L). In CSF ammonia was 29 µmol/L (range 17-55 µmol/L; difference from value in pus: p < 0.001). The total concentration of amino acids in brain abscesses was 1.12-16 times higher than the ammonia concentration (p = 0.011). The median glucose value in pus was 0 mmol/L (range 0-2.1 mmol/L), lactate was 21 mmol/L (range 3.3-26.5 mmol/L), and pH was 6.8 (range 6.2-7.3). In vitro, S. intermedius and S. aureus formed ammonia at 6-7 mmol/L in 24 hours when incubated with 20 proteinogenic amino acids plus g-aminobutyric acid (GABA), taurine, and glutathione at 1 mmol/L. CONCLUSIONS: Intracerebral abscesses contain toxic levels of ammonia. At the concentrations found in pus, ammonia could contribute to the brain edema and the symptoms of brain abscesses.

High extracellular levels of potassium and trace metals in human brain abscess.

Brain abscesses frequently cause symptoms such as seizures, delirium, paresis and sensory deficits that could reflect brain edema, increased intracranial pressure, or tissue destruction. However, it is also possible that pus constituents could disturb neuronal function in the surrounding brain tissue. In pus from 16 human brain abscesses, extracellular potassium ([K(+)]o) was 10.6 ± 4.8 mmol/L (mean ± SD; maximum value 22.0 mmol/L). In cerebrospinal fluid (CSF), [K(+)]o was 2.7 ± 0.6 mmol/L (N = 14; difference from pus p < 0.001), which is similar to previous control values for [K(+)]o in CSF and brain parenchyma. Zinc and iron were >40-fold higher in pus than in CSF; calcium, copper, manganese, and chromium were also higher, whereas sodium and magnesium were similar. Pus from 10 extracerebral abscesses (empyemas) also had higher [K(+)]o, zinc, iron, calcium, copper, manganese, and chromium than did CSF. Brain abscess [K(+)]o was significantly higher than serum potassium (3.8 ± 0.5 mmol/L; p = 0.0001), indicating that the elevated abscess [K(+)]o originated from damaged cells (e.g. brain cells and leukocytes), not from serum. High [K(+)]o could depolarize neurons, high levels of zinc could inhibit glutamate and GABA receptors, and high levels of iron and copper could cause oxidative damage, all of which could contribute to neuronal dysfunction in brain abscess patients.

Brain infection with Staphylococcus aureus leads to high extracellular levels of glutamate, aspartate, γ-aminobutyric acid, and zinc.

Staphylococcal brain infections may cause mental deterioration and epileptic seizures, suggesting interference with normal neurotransmission in the brain. We injected Staphylococcus aureus into rat striatum and found an initial 76% reduction in the extracellular level of glutamate as detected by microdialysis at 2 hr after staphylococcal infection. At 8 hr after staphylococcal infection, however, the extracellular level of glutamate had increased 12-fold, and at 20 hr it had increased >30-fold. The extracellular level of aspartate and γ-aminobutyric acid (GABA) also increased greatly. Extracellular Zn(2+) , which was estimated at ∼2.6 µmol/liter in the control situation, was increased by 330% 1-2.5 hr after staphylococcal infection and by 100% at 8 and 20 hr. The increase in extracellular glutamate, aspartate, and GABA appeared to reflect the degree of tissue damage. The area of tissue damage greatly exceeded the area of staphylococcal infiltration, pointing to soluble factors being responsible for cell death. However, the N-methyl-D-aspartate receptor antagonist MK-801 ameliorated neither tissue damage nor the increase in extracellular neuroactive amino acids, suggesting the presence of neurotoxic factors other than glutamate and aspartate. In vitro staphylococci incubated with glutamine and glucose formed glutamate, so bacteria could be an additional source of infection-related glutamate. We conclude that the dramatic increase in the extracellular concentration of neuroactive amino acids and zinc could interfere with neurotransmission in the surrounding brain tissue, contributing to mental deterioration and a predisposition to epileptic seizures, which are often seen in brain abscess patients.

High extracellular concentration of excitatory amino acids glutamate and aspartate in human brain abscess.

Brain abscesses often cause symptoms of brain dysfunction, including seizures, suggesting interference with normal neurotransmission. We determined the concentration of extracellular neuroactive amino acids in brain abscesses from 16 human patients. Glutamate was present at 3.6 mmol/L (median value, range 0.5-10.8), aspartate at 1.0 mmol/L (range 0.09-6.8). For comparison, in cerebroventricular fluid glutamate was ∼0.6 µmol/L, and aspartate was not different from zero. The total concentration of amino acids was higher in eight patients with seizures: 66 mmol/L (median value, range 19-109) vs. 21 mmol/L (range 4-52) in eight patients without seizures (p=0.026). The concentration of aspartate and essential amino acids tryptophan, phenylalanine, tyrosine, leucine, and isoleucine was higher in pus from patients with seizures (p⩽0.040), whereas that of glutamate was not (p=0.095). The median concentration of the non-proteinogenic, inhibitory amino acid taurine was similar in the two groups, 0.7-0.8 mmol/L (range 0.1-6.1). GABA could not be detected in pus. The patient groups did not differ with respect to abscess volume, the cerebral lobe affected, age, or time from symptom onset to surgery. Seven patients with extracerebral, intracranial abscesses had significantly lower pus concentration of glutamate (352 µmol/L, range 83-1368) and aspartate (71 µmol/L, range 22-330) than intracerebral abscesses (p<0.001). We conclude that excitatory amino acids glutamate and aspartate may reach very high concentrations in brain abscesses, probably contributing to symptoms through activation of glutamate receptors in the surrounding brain tissue.

Critical role for the AIM2 inflammasome during acute CNS bacterial infection.

Interleukin-1ß (IL-1ß) is essential for eliciting protective immunity during the acute phase of Staphylococcus aureus (S. aureus) infection in the central nervous system (CNS). We previously demonstrated that microglial IL-1ß production in response to live S. aureus is mediated through the Nod-like receptor protein 3 (NLRP3) inflammasome, including the adapter protein ASC (apoptosis-associated speck-like protein containing a caspase-1 recruitment domain), and pro-caspase 1. Here, we utilized NLRP3, ASC, and caspase 1/11 knockout (KO) mice to demonstrate the functional significance of inflammasome activity during CNS S. aureus infection. ASC and caspase 1/11 KO animals were exquisitely sensitive, with approximately 50% of mice succumbing to infection within 24 h. Unexpectedly, the survival of NLRP3 KO mice was similar to wild-type animals, suggesting the involvement of an alternative upstream sensor, which was later identified as absent in melanoma 2 (AIM2) based on the similar disease patterns between AIM2 and ASC KO mice. Besides IL-1ß, other key inflammatory mediators, including IL-6, CXCL1, CXCL10, and CCL2 were significantly reduced in the CNS of AIM2 and ASC KO mice, implicating autocrine/paracrine actions of IL-1ß, as these mediators do not require inflammasome processing for secretion. These studies demonstrate a novel role for the AIM2 inflammasome as a critical molecular platform for regulating IL-1ß release and survival during acute CNS S. aureus infection.

Escherichia coli brain abscess in a twin pair associated with TLR4 gene mutation.

Brain abscesses are uncommon complications of bacterial meningitis or sepsis in neonates and infants. The causative pathogens of brain abscess in newborns are various. Of those, Escherichia coli is rarely seen as a pathogen in brain abscess at this age. Herein we reported brain abscesses in twin infants caused by E. coli sepsis. Interestingly, genetic analysis identified heterozygous Toll-like receptor 4 (TLR4) gene mutation in the twins. Because TLR plays an important role in the natural response to bacterial products and initiates specific immune response against these pathogens, this may explain the development of brain abscess in the present case.

Application of 31P MR spectroscopy to the brain tumors.

OBJECTIVE: To evaluate the clinical feasibility and obtain useful parameters of (31)P magnetic resonance spectroscopy (MRS) study for making the differential diagnosis of brain tumors. MATERIALS AND METHODS: Twenty-eight patients with brain tumorous lesions (22 cases of brain tumor and 6 cases of abscess) and 11 normal volunteers were included. The patients were classified into the astrocytoma group, lymphoma group, metastasis group and the abscess group. We obtained the intracellular pH and the metabolite ratios of phosphomonoesters/phosophodiesters (PME/PDE), PME/inorganic phosphate (Pi), PDE/Pi, PME/adenosine triphosphate (ATP), PDE/ATP, PME/phosphocreatine (PCr), PDE/PCr, PCr/ATP, PCr/Pi, and ATP/Pi, and evaluated the statistical significances. RESULTS: The brain tumors had a tendency of alkalization (pH = 7.28 ± 0.27, p = 0.090), especially the pH of the lymphoma was significantly increased (pH = 7.45 ± 0.32, p = 0.013). The brain tumor group showed increased PME/PDE ratio compared with that in the normal control group (p = 0.012). The ratios of PME/PDE, PDE/Pi, PME/PCr and PDE/PCr showed statistically significant differences between each brain lesion groups (p < 0.05). The astrocytoma showed an increased PME/PDE and PME/PCr ratio. The ratios of PDE/Pi, PME/PCr, and PDE/PCr in lymphoma group were lower than those in the control group and astrocytoma group. The metastasis group showed an increased PME/PDE ratio, compared with that in the normal control group. CONCLUSION: We have obtained the clinically applicable (31)P MRS, and the pH, PME/PDE, PDE/Pi, PME/PCr, and PDE/PCr ratios are helpful for differentiating among the different types of brain tumors.

Proton MR spectroscopy in patients with pyogenic brain abscess: MR spectroscopic imaging versus single-voxel spectroscopy.

PURPOSE: Single-voxel spectroscopy (SVS) has been the gold standard technique to diagnose the pyogenic abssess. Two-dimensional magnetic resonance spectroscopic imaging (MRSI) is able to provide spatial distribution of metabolic concentration, and is potentially more suitable for differential diagnosis between abscess and necrotic tumors. Therefore, the purpose of this study was to evaluate the equivalence of MRSI and SVS in the detection of the metabolites in pyogenic brain abscesses. MATERIALS AND METHODS: Forty-two patients with pyogenic abscesses were studied by using both SVS and MRSI methods. Two neuroradiologists reviewed the MRS data independently. A κ value was calculated to express inter-reader agreement of the abscesses metabolites, and a correlation coefficient was calculated to show the similarity of two spectra. After consensus judgment of two readers, the binary value of metabolites of pyogenic abscesses (presence or absence) was compared between SVS and MRSI. RESULTS: The consistency of spectral interpretation of the two readers was very good (κ ranged from 0.95 to 1), and the similarity of two spectra was also very high (cc=0.9±0.05). After consensus judgment of two readers, the sensitivities of MRSI ranged from 91% (acetate) to 100% (amino acids, succinate, lactate, lipid), and the specificities of MRSI were 100% for detecting all metabolites with SVS as reference. CONCLUSION: SVS and MRSI provide similar metabolites in the cavity of pyogenic brain abscess. With additional metabolic information of cavity wall and contralateral normal-appearing brain tissue, MRSI would be a more suitable technique to differentiate abscesses from necrotic tumors.

Epidermoid cyst with a metabolite pattern mimicking a brain abscess. A magnetic resonance spectroscopy study.

BACKGROUND AND PURPOSE: Intracranial epidermal cysts are benign uncommon lesions. Such lesions arise from an inclusion of an ectodermal element during neural tube closure, in which dermal elements become trapped in the suture line, diploe, meninges, or scalp. Reports have extensively demonstrated the typical magnetic resonance (MR) spectra with the presence of large lactate signals with a virtual absence of healthy brain metabolites. METHODS: A 20-year-old male patient with a parietal lobe brain lesion was studied by magnetic resonance imaging and magnetic resonance spectroscopy in a 1.5-T Philips scanner. RESULTS: The lesion presented atypical MR spectra with presence of alanine (1.46 ppm), lactate (1.31 ppm), and amino acids such as valine, isoleucine (0.97 ppm), and glicine (3.52 ppm). No evidence of normal parenchyma tissue metabolites (N-acetylaspartate, creatine, and choline) or succinate and acetate signals was observed. This spectral pattern was unexpected being proposed the differential diagnosis of brain abscess versus epidermoid cyst. Finally, surgical total excision biopsy confirmed the diagnosis of epidermal cyst. CONCLUSIONS: In this report, we describe a case of an epidermal cyst with an unusual metabolic pattern observed by magnetic resonance spectroscopy mimicking a brain abscess.

IL-1RI (interleukin-1 receptor type I) signalling is essential for host defence and hemichannel activity during acute central nervous system bacterial infection.

Staphylococcus aureus is a common aetiological agent of bacterial brain abscesses. We have previously established that a considerable IL-1 (interleukin-1) response is elicited immediately following S. aureus infection, where the cytokine can exert pleiotropic effects on glial activation and blood-brain barrier permeability. To assess the combined actions of IL-1α and IL-1ß during CNS (central nervous system) infection, host defence responses were evaluated in IL-1RI (IL-1 receptor type I) KO (knockout) animals. IL-1RI KO mice were exquisitely sensitive to intracerebral S. aureus infection, as demonstrated by enhanced mortality rates and bacterial burdens within the first 24 h following pathogen exposure compared with WT (wild-type) animals. Loss of IL-1RI signalling also dampened the expression of select cytokines and chemokines, concomitant with significant reductions in neutrophil and macrophage infiltrates into the brain. In addition, the opening of astrocyte hemichannels during acute infection was shown to be dependent on IL-1RI activity. Collectively, these results demonstrate that IL-1RI signalling plays a pivotal role in the genesis of immune responses during the acute stage of brain abscess development through S. aureus containment, inflammatory mediator production, peripheral immune cell recruitment, and regulation of astrocyte hemichannel activity. Taken in the context of previous studies with MyD88 (myeloid differentiation primary response gene 88) and TLR2 (Toll-like receptor 2) KO animals, the current report advances our understanding of MyD88-dependent cascades and implicates IL-1RI signalling as a major antimicrobial effector pathway during acute brain-abscess formation.

Neuroinflammation leads to region-dependent alterations in astrocyte gap junction communication and hemichannel activity.

Inflammation attenuates gap junction (GJ) communication in cultured astrocytes. Here we used a well-characterized model of experimental brain abscess as a tool to query effects of the CNS inflammatory milieu on astrocyte GJ communication and electrophysiological properties. Whole-cell patch-clamp recordings were performed on green fluorescent protein (GFP)-positive astrocytes in acute brain slices from glial fibrillary acidic protein-GFP mice at 3 or 7 d after Staphylococcus aureus infection in the striatum. Astrocyte GJ communication was significantly attenuated in regions immediately surrounding the abscess margins and progressively increased to levels typical of uninfected brain with increasing distance from the abscess proper. Conversely, astrocytes bordering the abscess demonstrated hemichannel activity as evident by enhanced ethidium bromide (EtBr) uptake that could be blocked by several pharmacological inhibitors, including the connexin 43 (Cx43) mimetic peptide Gap26, carbenoxolone, the pannexin1 (Panx1) mimetic peptide (10)Panx1, and probenecid. However, hemichannel opening was transient with astrocytic EtBr uptake observed near the abscess at day 3 but not day 7 after infection. The region-dependent pattern of hemichannel activity at day 3 directly correlated with increases in Cx43, Cx30, Panx1, and glutamate transporter expression (glial L-glutamate transporter and L-glutamate/L-aspartate transporter) along the abscess margins. Changes in astrocyte resting membrane potential and input conductance correlated with the observed changes in GJ communication and hemichannel activity. Collectively, these findings indicate that astrocyte coupling and electrical properties are most dramatically affected near the primary inflammatory site and reveal an opposing relationship between the open states of GJ channels versus hemichannels during acute infection. This relationship may extend to other CNS diseases typified with an inflammatory component.